# gene_set_details

description_brief: Genes down-regulated in embryonic stem cells with BRCA1 [GeneID=672] loss of function (LOF).
systematic_name: M1568
exact_source: Table 1S
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_full:
  BRCA1 gene is a tumor suppressor for breast and ovarian cancers with the putative role in DNA repair and transcription. To characterize the role of BRCA1 in transcriptional regulation, we analyzed gene expression profiles of mouse embryonic stem cells deficient in BRCA1 using microarray technology. We found that loss of BRCA1 correlated with decreased expression of several groups of genes including stress response genes, cytoskeleton genes, and genes involved in protein synthesis and degradation. Previous study showed that BRCA1 is a transcriptional co-activator of p53 protein; however the majority of p53 target genes remained at the same expression levels in BRCA1 knockout cells as in the wild type cells. The only p53 target gene down-regulated with the loss of BRCA1 was 14-3-3 sigma, a major G(2)/M checkpoint control gene. Similar to cells with decreased 14-3-3 sigma activity, BRCA1-deficient cells were unable to sustain G(2)/M growth arrest after exposure to ionizing radiation. We find that BRCA1 induction of 14-3-3 sigma requires the presence of wild type p53 and can be regulated by a minimal p53 response element.


systematic_name: M1577
exact_source: Table 1: cluster 3
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Strongly up-regulated at 16-24 h during differentiation of 3T3-L1 cells (fibroblast) into adipocytes.

description_full:
[cell repeats an earlier one in this file: 2068 characters]


systematic_name: M1591
exact_source: Table 2: Cluster 5
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster 5: genes progressively up-regulated (peak at 24 h time point) during differentiation of 3T3-L1 fibroblasts into adipocytes in response to adipogenic hormones.

description_full:
  The molecular mechanisms that regulate cellular differentiation during development and throughout life are complex. It is now recognized that precise patterns of differentially expressed genes ultimately direct a particular cell toward a given lineage and many of these are regulated during the earliest stages of differentiation. Using a microarray-based expression analysis, we have examined gene expression profiles during the first 24 h of 3T3-L1 adipocyte differentiation. RNA was isolated at times 0, 2, 8, 16, and 24 h following stimulation of differentiation and hybridized in duplicate to high density Affymetrix microarray gene chips containing a series of 13,179 cDNA/expressed sequence tag (EST) probe sets. Two hundred and eighty-five cDNA/ESTs were shown to have at least a fivefold change in expression levels during this time course and both hierarchical and self-organizing map clustering analysis was performed to categorize them by expression profiles. Several genes known to be regulated during this time period were confirmed and Western blot analysis of the proteins encoded by some of the identified genes revealed expression profiles similar to their mRNA counterparts. As expected, many of the genes identified have not been examined in such a critical time period during adipogenesis and may well represent novel adipogenic mediators.


description_brief: Genes up-regulated in 3T3 cells (fibroblast) upon activation of JNK pathway.
systematic_name: M1596
exact_source: Table 2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_full:
  The c-Jun N-terminal kinases (JNKs) are encoded by three genes that yield 10 isoforms through alternative mRNA splicing. The roles of each JNK isoform in the many putative biological responses where the JNK pathway is activated are still unclear. To examine the cellular responses mediated by different JNK isoforms, gain-of-function JNK1 polypeptides were generated by fusing the upstream mitogen-activated protein kinase kinase, MKK7, with p46JNK1alpha or p46JNK1beta. The MKK7-JNK fusion proteins, which exhibited constitutive activity in 293T cells, were stably expressed in Swiss 3T3 fibroblasts using retrovirus-mediated gene transfer. Swiss 3T3 cells expressing either of the MKK7-JNK polypeptides were equally sensitized to induction of cell death following serum withdrawal. To search for other cellular responses that may be selectively regulated by the JNK1 isoforms, the gene expression profiles of Swiss 3T3 cells expressing MKK7-JNK1alpha or MKK7-JNK1beta were compared with empty vector-transfected control cells. Affymetrix Genechips identified 46 genes for which expression was increased in MKK7-JNK-expressing cells relative to vector control cells. Twenty genes including those for c-Jun, MKP-7, interluekin-1 receptor family member ST2L/ST2, and c-Jun-binding protein were induced similarly by MKK7-JNK1alpha and MKK7-JNK1beta proteins, whereas 13 genes were selectively increased by MKK7-JNK1alpha and 13 genes were selectively increased by MKK7-JNK1beta. The set of genes selectively induced by MKK7-JNK1beta included a number of known interferon-stimulated genes (ISG12, ISG15, IGTP, and GTPI). Consistent with these gene expression changes, Swiss 3T3 cells expressing MKK7-JNK1beta exhibited increased resistance to vesicular stomatitis virus-induced cell death. These findings reveal evidence for JNK isoform-selective gene regulation and support a role for distinct JNK isoforms in specific cellular responses.


systematic_name: M1597
exact_source: Table 2: Cluster 2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster 2: genes maximally expressed at 2 h time point during differentiation of 3T3-L1 fibroblasts into adipocytes (cluster 2) in response to adipogenic hormones.

description_full:
  The molecular mechanisms that regulate cellular differentiation during development and throughout life are complex. It is now recognized that precise patterns of differentially expressed genes ultimately direct a particular cell toward a given lineage and many of these are regulated during the earliest stages of differentiation. Using a microarray-based expression analysis, we have examined gene expression profiles during the first 24 h of 3T3-L1 adipocyte differentiation. RNA was isolated at times 0, 2, 8, 16, and 24 h following stimulation of differentiation and hybridized in duplicate to high density Affymetrix microarray gene chips containing a series of 13,179 cDNA/expressed sequence tag (EST) probe sets. Two hundred and eighty-five cDNA/ESTs were shown to have at least a fivefold change in expression levels during this time course and both hierarchical and self-organizing map clustering analysis was performed to categorize them by expression profiles. Several genes known to be regulated during this time period were confirmed and Western blot analysis of the proteins encoded by some of the identified genes revealed expression profiles similar to their mRNA counterparts. As expected, many of the genes identified have not been examined in such a critical time period during adipogenesis and may well represent novel adipogenic mediators.


systematic_name: M1604
exact_source: Table 2: Fold >= 2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in MEF cells (embryonic fibroblast) upon Cre-lox knockout of DNMT1 [GeneID=1786].

description_full:
  Cytosine methylation of mammalian DNA is essential for the proper epigenetic regulation of gene expression and maintenance of genomic integrity. To define the mechanism through which demethylated cells die, and to establish a paradigm for identifying genes regulated by DNA methylation, we have generated mice with a conditional allele for the maintenance DNA methyltransferase gene Dnmt1. Cre-mediated deletion of Dnmt1 causes demethylation of cultured fibroblasts and a uniform p53-dependent cell death. Mutational inactivation of Trp53 partially rescues the demethylated fibroblasts for up to five population doublings in culture. Oligonucleotide microarray analysis showed that up to 10% of genes are aberrantly expressed in demethylated fibroblasts. Our results demonstrate that loss of Dnmt1 causes cell-type-specific changes in gene expression that impinge on several pathways, including expression of imprinted genes, cell-cycle control, growth factor/receptor signal transduction and mobilization of retroelements.


description_brief: Genes highly expressed in prenatal hippocampus (cluster 1).
systematic_name: M5316
exact_source: Table 1S
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_full:
  We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.


systematic_name: M1605
exact_source: Table 1: cluster 4
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Progressively up-regulated from 8-48 h during differentiation of 3T3-L1 cells (fibroblast) into adipocytes.

description_full:
[cell repeats an earlier one in this file: 2068 characters]


systematic_name: M1610
exact_source: Appendix 1B
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  All significantly up-regulated genes in kidney glomeruli isolated from TCF21 [Gene ID=6943] knockout mice.

description_full:
  Mouse mutations have provided tremendous insights into the molecular basis of renal and glomerular development. However, genes often play important roles during multiple stages of nephrogenesis, making it difficult to determine the role of a gene in a specific cell lineage such as the podocyte. Conditional gene targeting and chimeric analysis are two possible approaches to dissect the function of genes in specific cell populations. However, these are labor-intensive and costly and require the generation, validation, and analysis of additional transgenic lines. For overcoming these shortcomings and, specifically, for studying the role of gene function in developing glomeruli, a technique to isolate and purify glomeruli from murine embryos was developed. Combined with gene expression profiling, this method was used to identify differentially expressed genes in glomeruli from Pod1 knockout (KO) mice that die in the perinatal period with multiple renal defects. Glomeruli from early developing stages (late S-shape/early capillary loop) onward can be isolated successfully from wild-type and KO kidneys at 18.5 d postcoitus, and RNA can readily be obtained and used for genome-wide microarray analysis. With this approach, 3986 genes that are differently expressed between glomeruli from Pod1 KO and wild-type mice were identified, including a four-fold reduction of alpha 8 integrin mRNA in glomeruli from Pod1 KO mice that was confirmed by immunostaining. This procedure may be adapted to any transgenic strain, providing a rapid and efficient method to dissect the function of specific genes in glomerular development.


systematic_name: M1611
exact_source: Table 1: Cpr-low/Cpr-lox >= 2
source_species_code: MM
GEO_id: GSE2362
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in liver from transgenic mice with reduced expression of POR [GeneID=5447] in all tissues.

description_full:
  NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-alpha by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice.


systematic_name: M1615
exact_source: Table 1: Cpr-low/Cpr-lox =< 0.5
source_species_code: MM
GEO_id: GSE2362
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in liver from transgenic mice with reduced expression of POR [GeneID=5447] in all tissues.

description_full:
  NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-alpha by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice.


systematic_name: M1623
exact_source: Table 4
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Down-regulated in murine dorsal skin cells at 6 h after treatment with the phorbol ester carcinogen TPA [PubChem=4792].

description_full:
  Malignant transformation of mouse skin by chemical carcinogens and tumour promoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process that leads to squamous cell carcinoma (SCC) formation. In an effort to identify tumour-associated genes, we studied the influence of short-term TPA-treatment on the gene expression profile of murine skin. A comprehensive microarray with some 5,000 murine gene specific cDNA fragments was established and hybridised with pooled RNA derived from control and TPA-treated dorsal skin samples. Of these genes, 54 were up- and 35 were down-regulated upon TPA application. Additionally, we performed suppression subtractive hybridisation (SSH) with respective RNA pools to generate and analyse a cDNA library enriched for TPA-inducible genes. Expression data of selected genes were confirmed by quantitative real-time PCR and Northern blot analysis. Comparison of microarray and SSH data revealed that 26% of up-regulated genes identified by expression profiling matched with those present in the SSH library. Besides numerous known genes, we identified a large set of unknown cDNAs that represent previously unrecognised TPA-regulated genes in murine skin with potential function in tumour promotion. Additionally, some TPA-induced genes, such as Sprr1A, Saa3, JunB, Il4ralpha, Gp38, RalGDS and Slpi exhibit high basal level in advanced stages of skin carcinogenesis, suggesting that at least a subgroup of the identified TPA-regulated genes may contribute to tumour progression and metastasis.


systematic_name: M1624
exact_source: Table 1
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in NIH 3T3 cells (fibroblasts) 24 h after inducing MYOD [GeneID=4654] which were down-regulated by dominant negative form of SMARCA4 [GeneID=6597].

description_full:
  The activation of muscle-specific gene expression requires the coordinated action of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in the presence or absence of a dominant-negative BRG1 ATPase demonstrated that approximately one-third of MyoD-induced genes were highly dependent on SWI/SNF enzymes. To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter. We found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner but that MyoD binding occurred subsequent to H4 modification and Brg1 interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory proteins did not bind to the myogenin promoter, thereby providing evidence for SWI/SNF-dependent activator binding. We observed that the homeodomain factor Pbx1, which cooperates with MyoD to stimulate myogenin expression, is constitutively bound to the myogenin promoter in a SWI/SNF-independent manner, suggesting a two-step mechanism in which MyoD initially interacts indirectly with the myogenin promoter and attracts chromatin-remodeling enzymes, which then facilitate direct binding by MyoD and other regulatory proteins.


systematic_name: M1625
exact_source: Table 1 & 2: Camptothecin
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes specifically down-regulated in FL5.12 cells (pro-B lymphocyte) by  camptothecin [PubChem=2538].

description_full:
[cell repeats an earlier one in this file: 1414 characters]


systematic_name: M1627
exact_source: Table 2: Fold <= -2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes down-regulated in MEF cells (embryonic fibroblast) upon Cre-lox knockout of DNMT1 [GeneID=1786].

description_full:
  Cytosine methylation of mammalian DNA is essential for the proper epigenetic regulation of gene expression and maintenance of genomic integrity. To define the mechanism through which demethylated cells die, and to establish a paradigm for identifying genes regulated by DNA methylation, we have generated mice with a conditional allele for the maintenance DNA methyltransferase gene Dnmt1. Cre-mediated deletion of Dnmt1 causes demethylation of cultured fibroblasts and a uniform p53-dependent cell death. Mutational inactivation of Trp53 partially rescues the demethylated fibroblasts for up to five population doublings in culture. Oligonucleotide microarray analysis showed that up to 10% of genes are aberrantly expressed in demethylated fibroblasts. Our results demonstrate that loss of Dnmt1 causes cell-type-specific changes in gene expression that impinge on several pathways, including expression of imprinted genes, cell-cycle control, growth factor/receptor signal transduction and mobilization of retroelements.


systematic_name: M1632
exact_source: Table 2: cluster 5
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Strongly down-regulated at 2-96 h during differentiation of 3T3-L1 cells (fibroblast) into adipocytes.

description_full:
[cell repeats an earlier one in this file: 2068 characters]


systematic_name: M1633
exact_source: Table 4
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in 3T3-L1 cells (adipocyte) by insulin [GeneID=3630] but displayed blunted response to insulin the insulin resistant cells.

description_full:
  We have employed microarray technology using RNA from normal 3T3-L1 adipocytes and from 3T3-L1 adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha to identify a new class of insulin-responsive genes. These genes continued to respond normally to insulin even though the adipocytes themselves were metabolically insulin-resistant, i.e. they displayed a significantly decreased rate of insulin-stimulated glucose uptake. Approximately 12,000 genes/expressed sequence tags (ESTs) were screened. Of these, 40 genes/ESTs were identified that became insulin-resistant as expected (e.g. Socs-3, junB, and matrix metalloproteinase-11). However, 61 genes/ESTs continued to respond normally to insulin. Although some of these genes were previously shown to be regulated by insulin (e.g. Glut-1 and beta3-adrenergic receptor), other novel insulin-sensitive genes were also identified (e.g. Egr-1, epiregulin, Fra-1, and ABCA1). Real-time reverse transcription-PCR analysis confirmed the expression patterns of several of the differentially expressed genes. One gene that remained insulin-sensitive in the insulin-resistant adipocytes is the transcription factor Egr-1. Using an antisense strategy, we show that tissue factor and macrophage colony-stimulating factor, two cardiovascular risk factors, are downstream EGR-1 target genes in the adipocyte. Taken together, these data support the hypothesis that some signaling pathways remain insulin-sensitive in metabolically insulin-resistant adipocytes. These pathways may promote abnormal gene expression in hyperinsulinemic states like obesity and type II diabetes and thus may contribute to pathologies associated with these conditions.


systematic_name: M1634
exact_source: Table 1: Liver-Cpr-null/Cpr-low >= 2
source_species_code: MM
GEO_id: GSE2362
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes up-regulated in liver from mice with liver specific knockout of POR [GeneID=5447] vs mice with reduced expression of POR in all tissues.

description_full:
  NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-alpha by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice.


description_brief: Genes down-regulated in MEF cells (embryonic fibroblasts) from PARP1 [GeneID=142] knockout mice.
systematic_name: M1642
exact_source: Table 1, 2: Fold <= -2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_full:
  Poly(ADP-ribose) polymerase (PARP) is implicated in the maintenance of genomic integrity, given that inhibition or depletion of this enzyme increases genomic instability in cells exposed to genotoxic agents. We previously showed that immortalized fibroblasts derived from PARP(-/-) mice exhibit an unstable tetraploid population, and partial chromosomal gains and losses in PARP(-/-) mice and immortalized fibroblasts are accompanied by changes in the expression of p53, Rb, and c-Jun, as well as other proteins. A tetraploid population has also now been detected in primary fibroblasts derived from PARP(-/-) mice. Oligonucleotide microarray analysis was applied to characterize more comprehensively the differences in gene expression between asynchronously dividing primary fibroblasts derived from PARP(-/-) mice and their wild-type littermates. Of the 11,000 genes monitored, 91 differentially expressed genes were identified. The loss of PARP results in down-regulation of the expression of several genes involved in regulation of cell cycle progression or mitosis, DNA replication, or chromosomal processing or assembly. PARP deficiency also up-regulates genes that encode extracellular matrix or cytoskeletal proteins that are implicated in cancer initiation or progression or in normal or premature aging. These results provide insight into the mechanism by which PARP deficiency impairs mitotic function, thereby resulting in the genomic alterations and chromosomal abnormalities as well as in altered expression of genes that may contribute to genomic instability, cancer, and aging.


systematic_name: M1645
exact_source: Table 1
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Adipocyte genes induced in 3T3-L1 cells (adipocyte) by constitutively active PPARG [GeneID=5468] or its agonist, TZD [PubChem=5437].

description_full:
  The PPARgamma is a key adipogenic determination factor. Ligands for PPARgamma such as antidiabetic thiazolidinedione (TZD) compounds are adipogenic, and many adipocyte genes that are activated by TZDs contain binding sites for PPARgamma. Like ligands for other nuclear receptors, TZDs can regulate genes positively or negatively. Here, we sought to understand the importance of positive regulation of gene expression by PPARgamma in adipogenesis. Fusion of the potent viral transcriptional activator VP16 to PPARgamma2 (VP16-PPARgamma) created a transcription factor that constitutively and dramatically activated transcription of PPARgamma-responsive genes in the absence of ligand. Forced expression of VP16-PPARgamma in 3T3-L1 preadipocytes using retroviral vectors led to adipogenesis in the absence of standard differentiating medium or any exogenous PPARgamma ligand. Gene microarray analysis revealed that VP16-PPARgamma induced many of the genes associated with adipogenesis and adipocyte function. Thus, direct up-regulation of gene expression by PPARgamma is sufficient for adipogenesis. TZD-induced adipogenesis up-regulated many of the same genes, although some were divergently regulated, including resistin, whose gene expression was reduced inVP16-PPARgamma adipocytes treated with TZDs. These results show that, although activation of PPARgamma by a heterologous activation domain is sufficient for adipogenesis, it is not equivalent to TZD treatment. This conclusion has important implications for understanding biological effects of the TZDs on adipogenesis and insulin sensitization.


systematic_name: M1648
exact_source: Table 2
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Genes most consistently regulated at 4 h by all six genotoxins tested: cisplatin, methyl methanesulfonate, mitomycin C, taxol, hydroxyurea and etoposide [PubChem=2767;4156;5746;4666;3657;36462].

description_full:
  During the safety evaluation process of new drugs and chemicals, a battery of genotoxicity tests is conducted starting with in vitro genotoxicity assays. Obtaining positive results in in vitro genotoxicity tests is not uncommon. Follow-up studies to determine the biological relevance of positive genotoxicity results are costly, time consuming, and utilize animals. More efficient methods, especially for identifying a putative mode of action like an indirect mechanism of genotoxicity (where DNA molecules are not the initial primary targets), would greatly improve the risk assessment for genotoxins. To this end, we are participating in an International Life Sciences Institute (ILSI) project involving studies of gene expression changes caused by model genotoxins. The purpose of the work is to evaluate gene expression tools in general, and specifically for discriminating genotoxins that are direct-acting from indirect-acting. Our lab has evaluated gene expression changes as well as micronuclei (MN) in L5178Y TK(+/-) mouse lymphoma cells treated with six compounds. Direct-acting genotoxins (where DNA is the initial primary target) that were evaluated included the DNA crosslinking agents, mitomycin C (MMC) and cisplatin (CIS), and an alkylating agent, methyl methanesulfonate (MMS). Indirect-acting genotoxins included hydroxyurea (HU), a ribonucleotide reductase inhibitor, taxol (TXL), a microtubule inhibitor, and etoposide (ETOP), a DNA topoisomerase II inhibitor. Microarray gene expression analysis was conducted using Affymetrix mouse oligonucleotide arrays on RNA samples derived from cells which were harvested immediately after the 4 h chemical treatment, and 20 h after the 4 h chemical treatment. The evaluation of these experimental results yields evidence of differentially regulated genes at both 4 and 24 h time points that appear to have discriminating power for direct versus indirect genotoxins, and therefore may serve as a fingerprint for classifying chemicals when their mechanism of action is unknown.


systematic_name: M1675
exact_source: Table 3: Clusters 19-32
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Selected genes up-regulated during differentiation of 3T3-L1 cells (fibroblast) into adipocytes in response to adipogenic hormones.

description_full:
  PPAR gamma is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR gamma, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR gamma agonist in vitro. The expression of 579 genes was significantly up- or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of beta-catenin as a new PPAR gamma target gene. Both mRNA and protein levels for beta-catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR gamma agonists. Treatment of db/db mice with a PPAR gamma agonist also resulted in reduction of beta-catenin mRNA levels in adipose tissue. These results suggest that beta-catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR gamma activation.


systematic_name: M1681
exact_source: Table 2: Cluster 4
source_species_code: MM
contributor: John Newman
contrib_organization: University of Washington
description_brief:
  Cluster 4: genes maximally expressed at 16 h time point during differentiation of 3T3-L1 fibroblasts into adipocytes in response to adipogenic hormones.

description_full:
[cell repeats an earlier one in this file: 1360 characters]


systematic_name: M1685
exact_source: Table 1S: MHS/LKR-13 co-cultures
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Proteins secreted in co-culture of LKR-13 tumor cells (non-small cell lung cancer, NSCLC) and MHS stroma cells (macrophages).

description_full:
  Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed stromal cells) that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.


systematic_name: M1686
exact_source: Table 1S: MEC/LKR-13 co-cultures
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Proteins secreted in co-culture of LKR-13 tumor cells (non-small cell lung cancer, NSCLC) and MEC stroma cells (endothelium).

description_full:
  Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed stromal cells) that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.


systematic_name: M1687
exact_source: Table 1S: MLg/LKR-13 co-cultures
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Proteins secreted in co-culture of LKR-13 tumor cells (non-small cell lung cancer, NSCLC) and MLg stroma cells (fibroblasts).

description_full:
  Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed stromal cells) that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.


description_brief: Selected genes down-regulated during invasion of lymphatic vessels during metastasis.
systematic_name: M11788
exact_source: Table 1: fold change < 0
source_species_code: MM
GEO_id: GSE6255
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Invasion of lymphatic vessels is a key step in the metastasis of primary tumors to draining lymph nodes. Although the process is enhanced by tumor lymphangiogenesis, it is unclear whether this is a consequence of increased lymphatic vessel number, altered lymphatic vessel properties, or both. Here we have addressed the question by comparing the RNA profiles of primary lymphatic endothelial cells (LEC) isolated from the vasculature of normal tissue and from highly metastatic T-241/vascular endothelial growth factor (VEGF)-C fibrosarcomas implanted in C57BL/6 mice. Our findings reveal significant differences in expression of some 792 genes (i.e., >or=2-fold up- or down-regulated, P <or= 0.05) that code for a variety of proteins including components of endothelial junctions, subendothelial matrix, and vessel growth/patterning. The tumor LEC profile, validated by immunohistochemical staining, is distinct from that of normal, inflammatory cytokine, or mitogen-activated LEC, characterized by elevated expression of such functionally significant molecules as the tight junction regulatory protein endothelial specific adhesion molecule (ESAM), the transforming growth factor-beta coreceptor Endoglin (CD105), the angiogenesis-associated leptin receptor, and the immunoinhibitory receptor CD200, and reduced expression of subendothelial matrix proteins including collagens, fibrillin, and biglycan. Moreover, we show similar induction of ESAM, Endoglin, and leptin receptor within tumor lymphatics in a series of human head and neck and colorectal carcinomas, and uncover a dramatic correlation between ESAM expression and nodal metastasis that identifies this marker as a possible prognostic indicator. These findings reveal a remarkable degree of phenotypic plasticity in cancer lymphatics and provide new insight into the processes of lymphatic invasion and lymph node metastasis.


description_brief: Genes from the brain cancer stem (cancer stem cell, CSC) signature.
systematic_name: M1694
exact_source: Table 1
source_species_code: MM
GEO_id: GSE13490
contributor: Leona Saunders
contrib_organization: MSigDB Team
description_full:
  The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.


systematic_name: M1719
exact_source: Table 1S: Choroid Plexus-enriched
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes enriched in choroid plexus cells in the brain identified through correlation-based searches seeded with the choroid plexus cell-type specific gene expression patterns.

description_full:
  Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.


systematic_name: M1729
exact_source: Fig 5S: cluster T4
source_species_code: MM
GEO_id: GSE7773,GSE7770,GSE7280
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cluster T4 of genes with similar expression profiles in thymic T lymphocytes after FOXP3 [GeneID=50943] loss of function (LOF).

description_full:
  Regulatory CD4+ T cells (Tr cells), the development of which is critically dependent on X-linked transcription factor Foxp3 (forkhead box P3), prevent self-destructive immune responses. Despite its important role, molecular and functional features conferred by Foxp3 to Tr precursor cells remain unknown. It has been suggested that Foxp3 expression is required for both survival of Tr precursors as well as their inability to produce interleukin (IL)-2 and independently proliferate after T-cell-receptor engagement, raising the possibility that such 'anergy' and Tr suppressive capacity are intimately linked. Here we show, by dissociating Foxp3-dependent features from those induced by the signals preceding and promoting its expression in mice, that the latter signals include several functional and transcriptional hallmarks of Tr cells. Although its function is required for Tr cell suppressor activity, Foxp3 to a large extent amplifies and fixes pre-established molecular features of Tr cells, including anergy and dependence on paracrine IL-2. Furthermore, Foxp3 solidifies Tr cell lineage stability through modification of cell surface and signalling molecules, resulting in adaptation to the signals required to induce and maintain Tr cells. This adaptation includes Foxp3-dependent repression of cyclic nucleotide phosphodiesterase 3B, affecting genes responsible for Tr cell homeostasis.


systematic_name: M1734
exact_source: Fig 5S: cluster P4
source_species_code: MM
GEO_id: GSE7770,GSE7280,GSE7773
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cluster P4 of genes with similar expression profiles in peripheral T lymphocytes after FOXP3 [GeneID=50943] loss of function (LOF).

description_full:
  Regulatory CD4+ T cells (Tr cells), the development of which is critically dependent on X-linked transcription factor Foxp3 (forkhead box P3), prevent self-destructive immune responses. Despite its important role, molecular and functional features conferred by Foxp3 to Tr precursor cells remain unknown. It has been suggested that Foxp3 expression is required for both survival of Tr precursors as well as their inability to produce interleukin (IL)-2 and independently proliferate after T-cell-receptor engagement, raising the possibility that such 'anergy' and Tr suppressive capacity are intimately linked. Here we show, by dissociating Foxp3-dependent features from those induced by the signals preceding and promoting its expression in mice, that the latter signals include several functional and transcriptional hallmarks of Tr cells. Although its function is required for Tr cell suppressor activity, Foxp3 to a large extent amplifies and fixes pre-established molecular features of Tr cells, including anergy and dependence on paracrine IL-2. Furthermore, Foxp3 solidifies Tr cell lineage stability through modification of cell surface and signalling molecules, resulting in adaptation to the signals required to induce and maintain Tr cells. This adaptation includes Foxp3-dependent repression of cyclic nucleotide phosphodiesterase 3B, affecting genes responsible for Tr cell homeostasis.


systematic_name: M1735
exact_source: Fig 5S: cluster P6
source_species_code: MM
GEO_id: GSE7770,GSE7773,GSE7280
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cluster P6 of genes with similar expression profiles in peripheral T lymphocytes after FOXP3 [GeneID=50943] loss of function (LOF).

description_full:
  Regulatory CD4+ T cells (Tr cells), the development of which is critically dependent on X-linked transcription factor Foxp3 (forkhead box P3), prevent self-destructive immune responses. Despite its important role, molecular and functional features conferred by Foxp3 to Tr precursor cells remain unknown. It has been suggested that Foxp3 expression is required for both survival of Tr precursors as well as their inability to produce interleukin (IL)-2 and independently proliferate after T-cell-receptor engagement, raising the possibility that such 'anergy' and Tr suppressive capacity are intimately linked. Here we show, by dissociating Foxp3-dependent features from those induced by the signals preceding and promoting its expression in mice, that the latter signals include several functional and transcriptional hallmarks of Tr cells. Although its function is required for Tr cell suppressor activity, Foxp3 to a large extent amplifies and fixes pre-established molecular features of Tr cells, including anergy and dependence on paracrine IL-2. Furthermore, Foxp3 solidifies Tr cell lineage stability through modification of cell surface and signalling molecules, resulting in adaptation to the signals required to induce and maintain Tr cells. This adaptation includes Foxp3-dependent repression of cyclic nucleotide phosphodiesterase 3B, affecting genes responsible for Tr cell homeostasis.


systematic_name: M1736
exact_source: Fig 5S: cluster P7
source_species_code: MM
GEO_id: GSE7773,GSE7770,GSE7280
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cluster P7 of genes with similar expression profiles in peripheral T lymphocytes after FOXP3 [GeneID=50943] loss of function (LOF).

description_full:
[cell repeats an earlier one in this file: 1399 characters]


systematic_name: M1739
exact_source: Supplementary Fig 7D
source_species_code: MM
GEO_id: GSE7773,GSE7280,GSE7770
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  FOXP3 [GeneID=50943] target genes up-regulated in T lymphocytes after stimulation with IL2 [GeneID=3558].

description_full:
[cell repeats an earlier one in this file: 1399 characters]


systematic_name: M1753
exact_source: Table 3S: thymus and periphery
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters bound by FOXP3 [GeneID=50943] and which are up-regulated both in developing (located in the thymus) and mature (from peripheral blood) regulatory CD4+ [GeneID=920] T lymphocytes.

description_full:
  Transcription factor Foxp3 (forkhead box P3), restricted in its expression to a specialized regulatory CD4+ T-cell subset (T(R)) with a dedicated suppressor function, controls T(R) lineage development. In humans and mice, Foxp3 deficiency results in a paucity of T(R) cells and a fatal breach in immunological tolerance, causing highly aggressive multi-organ autoimmune pathology. Here, through genome-wide analysis combining chromatin immunoprecipitation with mouse genome tiling array profiling, we identify Foxp3 binding regions for approximately 700 genes and for an intergenically encoded microRNA. We find that a large number of Foxp3-bound genes are up- or downregulated in Foxp3+ T cells, suggesting that Foxp3 acts as both a transcriptional activator and repressor. Foxp3-mediated regulation unique to the thymus affects, among others, genes encoding nuclear factors that control gene expression and chromatin remodelling. In contrast, Foxp3 target genes shared by the thymic and peripheral T(R) cells encode primarily plasma membrane proteins, as well as cell signalling proteins. Together, our studies suggest that distinct transcriptional sub-programmes implemented by Foxp3 establish T(R) lineage during differentiation and its proliferative and functional competence in the periphery.


systematic_name: M12676
exact_source: Table 1S: Class T genes: (N+L)/(T+L) > 3
source_species_code: MM
GEO_id: GSE7348
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Class NT (non-tolerizeable) genes: induced during the first LPS stimulation and induced at equal or greater degree in tolerant macrophages.

description_full:
  Toll-like receptors (TLRs) induce a multi-component inflammatory response that must be tightly regulated to avoid tissue damage. Most known regulatory mechanisms target TLR signalling pathways and thus broadly inhibit multiple aspects of the inflammatory response. Given the functional diversity of TLR-induced genes, we proposed that additional, gene-specific regulatory mechanisms exist to allow individual aspects of the TLR-induced response to be differentially regulated. Using an in vitro system of lipopolysaccharide tolerance in murine macrophages, we show that TLR-induced genes fall into two categories on the basis of their functions and regulatory requirements. We demonstrate that representatives from the two classes acquire distinct patterns of TLR-induced chromatin modifications. These gene-specific chromatin modifications are associated with transient silencing of one class of genes, which includes pro-inflammatory mediators, and priming of the second class, which includes antimicrobial effectors. These findings illustrate an adaptive response in macrophages and reveal component-specific regulation of inflammation.


systematic_name: M1761
exact_source: Table 1S: EpiSC d3
source_species_code: MM
GEO_id: GSE7902
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in EpiSC cells (mouse epiblast embryonic stem cells) after treatment with the ALK [GeneID=238] inhibitor SB-431542 [PubChem=4521392].

description_full:
[cell repeats an earlier one in this file: 1234 characters]


systematic_name: M1762
exact_source: Table 1S: EpiSC d4
source_species_code: MM
GEO_id: GSE7902
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in EpiSC cells (epiblast stem cells) after treatment with the ALK [GeneID=238] inhibitor SB-431542 [PubChem=4521392].

description_full:
[cell repeats an earlier one in this file: 1234 characters]


systematic_name: M1763
exact_source: Table 1S: mES d4 +SB431542 & JAK Inh.
source_species_code: MM
GEO_id: GSE7902
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in mES cells (mouse embryonic stem cells) after tratment with the ALK [GeneID=238] inhibitor SB-431542 and JAK inhibitor I [PubChem=4521392;5494425].

description_full:
[cell repeats an earlier one in this file: 1234 characters]


systematic_name: M1767
exact_source: Fig 5S: Cluster B
source_species_code: MM
GEO_id: GSE6135
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cluster B: genes down-regulated in primary lung tumors driven by KRAS [GeneID=3845] activation and loss of STK11 [GeneID=6794]; also up-regulated in human squamous cell carcinoma (SCC) vs adenocarcinoma subtype of NSCLC (non-small cell lung cancer).

description_full:
  Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.


description_brief: Genes down-regulated after cre-lox knockout of GATA6 [GeneID=2627] in airway epithelium.
systematic_name: M1778
exact_source: Fig 4a
source_species_code: MM
GEO_id: GSE11165
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta-catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.


description_brief: Genes down-regulated by hemizygotic cre-lox knockout of RSP6 [GeneID=81492] in keratinocytes.
systematic_name: M1781
exact_source: Table 1S
source_species_code: MM
GEO_id: GSE11331
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Mutations in genes encoding ribosomal proteins cause the Minute phenotype in Drosophila and mice, and Diamond-Blackfan syndrome in humans. Here we report two mouse dark skin (Dsk) loci caused by mutations in Rps19 (ribosomal protein S19) and Rps20 (ribosomal protein S20). We identify a common pathophysiologic program in which p53 stabilization stimulates Kit ligand expression, and, consequently, epidermal melanocytosis via a paracrine mechanism. Accumulation of p53 also causes reduced body size and erythrocyte count. These results provide a mechanistic explanation for the diverse collection of phenotypes that accompany reduced dosage of genes encoding ribosomal proteins, and have implications for understanding normal human variation and human disease.


systematic_name: M15626
exact_source: Table 1: Fold change > 0
source_species_code: MM
GEO_id: GSE11836
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated during prostate cancer progression in mice heterozygotic for both NKX3.1 and PTEN [GeneID=4824;5728].

description_full:
  To identify biomarkers that discriminate the aggressive forms of prostate cancer, we performed gene expression profiling of prostate tumors using a genetically engineered mouse model that recapitulates the stages of human prostate cancer, namely Nkx3.1; Pten mutant mice. We observed a significant deregulation of the epidermal growth factor and mitogen-activated protein kinase (MAPK) signaling pathways, as well as their major downstream effectors--the activator protein-1 transcription factors c-Fos and c-Jun. Forced expression of c-Fos and c-Jun in prostate cancer cells promotes tumorigenicity and results in activation of extracellular signal-regulated kinase (Erk) MAPK signaling. In human prostate cancer, up-regulation of c-Fos and c-Jun proteins occurs in advanced disease and is correlated with Erk MAPK pathway activation, whereas high levels of c-Jun expression are associated with disease recurrence. Our analyses reveal a hitherto unappreciated role for AP-1 transcription factors in prostate cancer progression and identify c-Jun as a marker of high-risk prostate cancer. This study provides a striking example of how accurate mouse models can provide insights on molecular processes involved in progression and recurrence of human cancer.


description_brief: Up-regulated genes defining rejection of mammary carcinoma (MMC) tumors.
systematic_name: M1787
exact_source: Table 1-2: Reject > Control
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  We have previously shown T-cell-mediated rejection of the neu-overexpressing mammary carcinoma cells (MMC) in wild-type FVB mice. However, following rejection of primary tumors, a fraction of animals experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (tumor evasion model) after a long latency period. In the present study, we determined that T cells derived from wild-type FVB mice can specifically recognize MMC by secreting IFN-gamma and can induce apoptosis of MMC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors and cannot reject it (tumor tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC tumors, we compared transcriptional patterns within the tumor microenvironment of MMC undergoing rejection with those that resisted it either because of tumor evasion/antigen loss recurrence (ANV tumors) or because of intrinsic tolerance mechanisms displayed by the transgenic mice. Gene profiling confirmed that immune rejection is primarily mediated through activation of IFN-stimulated genes and T-cell effector mechanisms. The tumor evasion model showed combined activation of Th1 and Th2 with a deviation toward Th2 and humoral immune responses that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials.


systematic_name: M1790
exact_source: Table 1: fold expression change > 0
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Epithelial and mesenchymal markers up-regulated in MEF cells (embryonic fibroblasts) after knockout of PRKAR1A [GeneID=5573].

description_full:
  Dysregulation of protein kinase A (PKA) activity, caused by loss of function mutations in PRKAR1A, is known to induce tumor formation in the inherited tumor syndrome Carney complex (CNC) and is also associated with sporadic tumors of the thyroid and adrenal. We have previously shown that Prkar1a(+/-) mice develop schwannomas reminiscent of those seen in CNC and that similar tumors are observed in tissue-specific knockouts (KO) of Prkar1a targeted to the neural crest. Within these tumors, we have previously described the presence of epithelial islands, although the nature of these structures was unclear. In this article, we report that these epithelial structures are derived from KO cells originating in the neural crest. Analysis of the mesenchymal marker vimentin revealed that this protein was markedly down-regulated not only from the epithelial islands, but also from the tumor as a whole, consistent with mesenchymal-to-epithelial transition (MET). In vitro, Prkar1a null primary mouse embryonic fibroblasts, which display constitutive PKA signaling, also showed evidence for MET, with a loss of vimentin and up-regulation of the epithelial marker E-cadherin. Reduction of vimentin protein occurred at the posttranslational level and was rescued by proteasomal inhibition. Finally, this down-regulation of vimentin was recapitulated in the adrenal nodules of CNC patients, confirming an unexpected and previously unrecognized role for PKA in MET.


systematic_name: M1796
exact_source: Table 2S
source_species_code: MM
GEO_id: GSE12694
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  The glioblastoma multiforme (GBM) plasticity signature: genes up-regulated in neural stem cells (NSC) with double knockout of TP53 and PTEN [GeneID=7157;5728] vs those with knockout of TP53 alone.

description_full:
  Glioblastoma (GBM) is a highly lethal brain tumour presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as a high-grade disease that typically harbours mutations in EGFR, PTEN and INK4A/ARF (also known as CDKN2A), and the secondary GBM subtype evolves from the slow progression of a low-grade disease that classically possesses PDGF and TP53 events. Here we show that concomitant central nervous system (CNS)-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with notable clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted TP53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of TP53 as well as the expected PTEN mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives increased Myc protein levels and its associated signature. Functional studies validated increased Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of NSCs doubly null for p53 and Pten (p53(-/-) Pten(-/-)) as well as tumour neurospheres (TNSs) derived from this model. Myc also serves to maintain robust tumorigenic potential of p53(-/-) Pten(-/-) TNSs. These murine modelling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumour suppressor mutation profile in human primary GBM and establish Myc as an important target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential.


systematic_name: M1798
exact_source: Table 1S
source_species_code: MM
GEO_id: GSE10167
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in E8.5 embryos with heterozygous knockout of TCOF1 [GeneID=6949] compared to wild type.

description_full:
  Treacher Collins syndrome (TCS) is a congenital disorder of craniofacial development arising from mutations in TCOF1, which encodes the nucleolar phosphoprotein Treacle. Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1-mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural crest cell hypoplasia characteristic of TCS. Here we show that inhibition of p53 prevents cyclin G1-driven apoptotic elimination of neural crest cells while rescuing the craniofacial abnormalities associated with mutations in Tcof1 and extending life span. These improvements, however, occur independently of the effects on ribosome biogenesis; thus suggesting that it is p53-dependent neuroepithelial apoptosis that is the primary mechanism underlying the pathogenesis of TCS. Our work further implies that neuroepithelial and neural crest cells are particularly sensitive to cellular stress during embryogenesis and that suppression of p53 function provides an attractive avenue for possible clinical prevention of TCS craniofacial birth defects and possibly those of other neurocristopathies.


description_brief: Direct targets of FOXA2 [GeneID=3170] in liver, according to a ChIP-chip analysis.
systematic_name: M1806
exact_source: Table 1S
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Production of bile by the liver is crucial for the absorption of lipophilic nutrients. Dysregulation of bile acid homeostasis can lead to cholestatic liver disease and endoplasmic reticulum (ER) stress. We show by global location analysis ('ChIP-on-chip') and cell type-specific gene ablation that the winged helix transcription factor Foxa2 is required for normal bile acid homeostasis. As suggested by the location analysis, deletion of Foxa2 in hepatocytes in mice using the Cre-lox system leads to decreased transcription of genes encoding bile acid transporters on both the basolateral and canalicular membranes, resulting in intrahepatic cholestasis. Foxa2-deficient mice are strikingly sensitive to a diet containing cholic acid, which results in toxic accumulation of hepatic bile salts, ER stress and liver injury. In addition, we show that expression of FOXA2 is markedly decreased in liver samples from individuals with different cholestatic syndromes, suggesting that reduced FOXA2 abundance could exacerbate the injury.


systematic_name: M1832
exact_source: Fig. 5: Spermatids
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes important for spermatid differentiation, based on mouse models with male reproductive defects.

description_full:
[cell repeats an earlier one in this file: 1515 characters]


systematic_name: M1844
exact_source: Suppl. Data
source_species_code: MM
GEO_id: GSE4114,GSE4767
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes in breast tumors from transgenic mice overexpressing ERBB2 and CDC25A [GeneID=2064;993] compared to those from mice overexpressing ERBB2 only.

description_full:
  Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint pathways are likely to serve as a tumor-suppressive barrier in vivo. The cell cycle-promoting phosphatase CDC25A is an activator of cyclin-dependent kinases and one of the downstream targets for the CHK1-mediated checkpoint pathway. Whereas CDC25A overexpression is observed in various human cancer tissues, it has not been determined whether deregulated CDC25A expression triggers or promotes tumorigenesis in vivo. Here, we show that transgenic expression of CDC25A cooperates markedly with oncogenic ras or neu in murine mammary tumorigenesis. MMTV-CDC25A transgenic mice exhibit alveolar hyperplasia in the mammary tissue but do not develop spontaneous mammary tumors. The MMTV-CDC25A transgene markedly shortens latency of tumorigenesis in MMTV-ras mice. The MMTV-CDC25A transgene also accelerates tumor growth in MMTV-neu mice with apparent cell cycle miscoordination. CDC25A-overexpressing tumors, which invade more aggressively, exhibit various chromosomal aberrations on fragile regions, including the mouse counterpart of human 1p31-36, according to array-based comparative genomic hybridization and karyotyping. The chromosomal aberrations account for substantial changes in gene expression profile rendered by transgenic expression of CDC25A, including down-regulation of Trp73. These data indicate that deregulated control of cellular CDC25A levels leads to in vivo genomic instability, which cooperates with the neu-ras oncogenic pathway in mammary tumorigenesis.


systematic_name: M1845
exact_source: Suppl. Data
source_species_code: MM
GEO_id: GSE4114,GSE4767
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Down-regulated genes in breast tumors from transgenic mice overexpressing ERBB2 and CDC25A [GeneID=2064;993] compared to those from mice overexpressing ERBB2 only.

description_full:
  Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint pathways are likely to serve as a tumor-suppressive barrier in vivo. The cell cycle-promoting phosphatase CDC25A is an activator of cyclin-dependent kinases and one of the downstream targets for the CHK1-mediated checkpoint pathway. Whereas CDC25A overexpression is observed in various human cancer tissues, it has not been determined whether deregulated CDC25A expression triggers or promotes tumorigenesis in vivo. Here, we show that transgenic expression of CDC25A cooperates markedly with oncogenic ras or neu in murine mammary tumorigenesis. MMTV-CDC25A transgenic mice exhibit alveolar hyperplasia in the mammary tissue but do not develop spontaneous mammary tumors. The MMTV-CDC25A transgene markedly shortens latency of tumorigenesis in MMTV-ras mice. The MMTV-CDC25A transgene also accelerates tumor growth in MMTV-neu mice with apparent cell cycle miscoordination. CDC25A-overexpressing tumors, which invade more aggressively, exhibit various chromosomal aberrations on fragile regions, including the mouse counterpart of human 1p31-36, according to array-based comparative genomic hybridization and karyotyping. The chromosomal aberrations account for substantial changes in gene expression profile rendered by transgenic expression of CDC25A, including down-regulation of Trp73. These data indicate that deregulated control of cellular CDC25A levels leads to in vivo genomic instability, which cooperates with the neu-ras oncogenic pathway in mammary tumorigenesis.


description_brief: Genes down-regulated in neurons after NPAS4 [GeneID=266743] knockdown by RNAi.
systematic_name: M7327
exact_source: Table 1S: D = Down-regulated
source_species_code: MM
GEO_id: GSE11258,GSE11256,GSE11261
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.


systematic_name: M5688
exact_source: Table 1S
source_species_code: MM
GEO_id: GSE12707,GSE13512
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in Paneth cell (part of intestiinal epithelium) of mice with hypomorphic (reduced function) form of ATG16L1 [GeneID=55054].

description_full:
  Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.


systematic_name: M13796
exact_source: Table 2S: upregulated genes
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in a mouse model of heart disease whose expression reverted to normal by silencing of MIR21 [GeneID=406991] microRNA.

description_full:
  MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.


systematic_name: M18073
exact_source: Table 2S: downregulated genes
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in a mouse model of heart disease whose expression reverted to normal by silencing of MIR21 [GeneID=406991] microRNA.

description_full:
  MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.


systematic_name: M15228
exact_source: Fig. 3bS
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in naive T lymphocytes lacking FURIN [GeneID=5045]: Cre-Lox knockout of FURIN in CD4+ [GeneID=920] cells.

description_full:
  West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem. However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited. WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection. WNV enters the cytoplasm through pH-dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway. RNA interference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions. Here we report the identification of 305 host proteins that affect WNV infection, using a human-genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post-entry role for the endoplasmic-reticulum-associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV-human cell interactions that forms a model for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets.


systematic_name: M9331
exact_source: Supplmentary File 2: pvalue<0.05 and log2(Fold Change) < -1.5
source_species_code: MM
GEO_id: GSE11981
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in mouse stroma of pancreatic adenocarcinoma zenografts after treatment with HhAntag, a hedgehog (Hh) pathway inhibitor.

description_full:
  Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.


description_brief: Transcription factors expressed in progenitors of exocrine pancreatic cells.
systematic_name: M1860
exact_source: Table 1S: pancreatic progenitor
source_species_code: MM
GEO_id: GSE12025
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.


systematic_name: M1865
exact_source: Table 2S: Invasive/general >= 2
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Up-regulated genes in the subpopulation of invasive PyMT cells (breast cancer) compared to the general population of PyMT cells.

description_full:
  Correlating tumor cell behavior in vivo with patterns of gene expression has led to new insights into the microenvironment of tumor cells in the primary tumor. Until now, these studies have been done with cell line-derived tumors. In the current study, we have analyzed, in polyoma middle T oncogene (PyMT)-derived mammary tumors, tumor cell behavior and gene expression patterns of the invasive subpopulation of tumor cells by multiphoton-based intravital imaging and microarray-based expression profiling, respectively. Our results indicate that the patterns of cell behavior that contribute to invasion and metastasis in the PyMT tumor are similar to those seen previously in rat MTLn3 cell line-derived mammary tumors. The invasive tumor cells collected from PyMT mouse mammary tumors, like their counterparts from rat xenograft mammary tumors, are a population that is relatively nondividing and nonapoptotic but chemotherapy resistant and chemotactic. Changes in the expression of genes that occur uniquely in the invasive subpopulation of tumor cells in the PyMT mammary tumors that fall on the Arp2/3 complex, capping protein and cofilin pathways show a pattern like that seen previously in invasive tumor cells from the MTLn3 cell line-derived tumors. These changes predict an enhanced activity of the cofilin pathway, and this was confirmed in isolated invasive PyMT tumor cells. We conclude that changes in gene expression and their related changes in cell behavior, which were identified in the invasive tumor cells of cell line-derived tumors, are conserved in the invasive tumor cells of PyMT-derived mouse mammary tumors, although these tumor types have different genetic origins.


description_brief: Genes up-regulated in bone marrow progenitors by constitutively active NOTCH1 [GeneID=4851].
systematic_name: M1869
exact_source: Fig 1a, 1BS, 1CS: up in either early or late
source_species_code: MM
GEO_id: GSE6396
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced neoplastic transformation remain undefined. We report here that constitutively active Notch1 activates the NF-kappaB pathway transcriptionally and via the IkappaB kinase (IKK) complex, thereby causing increased expression of several well characterized target genes of NF-kappaB in bone marrow hematopoietic stem cells and progenitors. Our observations demonstrate that the NF-kappaB pathway is highly active in established human T-ALL and that inhibition of the pathway can efficiently restrict tumor growth both in vitro and in vivo. These findings identify NF-kappaB as one of the major mediators of Notch1-induced transformation and suggest that the NF-kappaB pathway is a potential target of future therapies of T-ALL.


systematic_name: M1875
exact_source: Table 1S
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Cytokines, growth factors, and secreted proteins that show increased expression on a protein array of samples from aged TERC [GeneID=7012] knockout mice.

description_full:
  Cell-intrinsic checkpoints limit the proliferative capacity of primary cells in response to telomere dysfunction. It is not known, however, whether telomere dysfunction contributes to cell-extrinsic alterations that impair stem cell function and organ homeostasis. Here we show that telomere dysfunction provokes defects of the hematopoietic environment that impair B lymphopoiesis but increase myeloid proliferation in aging telomerase knockout (Terc(-/-)) mice. Moreover, the dysfunctional environment limited the engraftment of transplanted wild-type hematopoietic stem cells (HSCs). Dysfunction of the hematopoietic environment was age dependent and correlated with progressive telomere shortening in bone marrow stromal cells. Telomere dysfunction impaired mesenchymal progenitor cell function, reduced the capacity of bone marrow stromal cells to maintain functional HSCs, and increased the expression of various cytokines, including granulocyte colony-stimulating factor (G-CSF), in the plasma of aging mice. Administration of G-CSF to wild-type mice mimicked some of the defects seen in aging Terc(-/-) mice, including impairment of B lymphopoiesis and HSC engraftment. Conversely, inhibition of G-CSF improved HSC engraftment in aged Terc(-/-) mice. Taken together, these results show that telomere dysfunction induces alterations of the environment that can have implications for organismal aging and cell transplantation therapies.


description_brief: An assortment of osteoblast transcriptional regulators.
systematic_name: M6267
exact_source: Table 2
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_full:
  The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, and to exploit these molecules for therapeutic purposes. New insights into the pathophysiology of diseases have also enabled us to understand molecular defects in a way that was not possible a decade ago. This review summarizes our current understanding of the carefully orchestrated cross-talk between cells of the bone marrow and between bone cells and the brain through which bone is constantly remodeled during adult life. It also highlights molecular aberrations that cause bone cells to become dysfunctional, as well as therapeutic options and opportunities to counteract skeletal loss.


systematic_name: M11290
exact_source: Fig. 1aS
source_species_code: MM
GEO_id: GSE4356
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Chemokine genes up-regulated within 2 hr of c-Myc [GeneID=4609] activation in a mouse model of Myc-induced pancreatic beta-cell tumorigenesis.

description_full:
  An association between inflammation and cancer has long been recognized, but the cause and effect relationship linking the two remains unclear. Myc is a pleiotropic transcription factor that is overexpressed in many human cancers and instructs many extracellular aspects of the tumor tissue phenotype, including remodeling of tumor stroma and angiogenesis. Here we show in a beta-cell tumor model that activation of Myc in vivo triggers rapid recruitment of mast cells to the tumor site-a recruitment that is absolutely required for macroscopic tumor expansion. In addition, treatment of established beta-cell tumors with a mast cell inhibitor rapidly triggers hypoxia and cell death of tumor and endothelial cells. Inhibitors of mast cell function may therefore prove therapeutically useful in restraining expansion and survival of pancreatic and other cancers.


systematic_name: M7245
exact_source: Table 1S: Fold change > 2
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in hepatic stellar cells after stimulation with bacterial lipopolysacharide (LPS).

description_full:
  Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products. Here we report that the intestinal bacterial microflora and a functional Toll-like receptor 4 (TLR4), but not TLR2, are required for hepatic fibrogenesis. Using Tlr4-chimeric mice and in vivo lipopolysaccharide (LPS) challenge, we demonstrate that quiescent hepatic stellate cells (HSCs), the main precursors for myofibroblasts in the liver, are the predominant target through which TLR4 ligands promote fibrogenesis. In quiescent HSCs, TLR4 activation not only upregulates chemokine secretion and induces chemotaxis of Kupffer cells, but also downregulates the transforming growth factor (TGF)-beta pseudoreceptor Bambi to sensitize HSCs to TGF-beta-induced signals and allow for unrestricted activation by Kupffer cells. LPS-induced Bambi downregulation and sensitization to TGF-beta is mediated by a MyD88-NF-kappaB-dependent pathway. Accordingly, Myd88-deficient mice have decreased hepatic fibrosis. Thus, modulation of TGF-beta signaling by a TLR4-MyD88-NF-kappaB axis provides a novel link between proinflammatory and profibrogenic signals.


systematic_name: M1880
exact_source: Table 3S
source_species_code: MM
GEO_id: GSE9167
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated during later stages of renal maturation (days P14-P16) in kidney specific knockout of PKD1 [GeneID=5310].

description_full:
  Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesis is an ongoing process during adult life. We now show that inactivation of Pkd1 in mice before postnatal day 13 results in severely cystic kidneys within 3 weeks, whereas inactivation at day 14 and later results in cysts only after 5 months. We found that cellular proliferation was not appreciably higher in cystic specimens than in age-matched controls, but the abrupt change in response to Pkd1 inactivation corresponded to a previously unrecognized brake point during renal growth and significant changes in gene expression. These findings suggest that the effects of Pkd1 inactivation are defined by a developmental switch that signals the end of the terminal renal maturation process. Our studies show that Pkd1 regulates tubular morphology in both developing and adult kidney, but the pathologic consequences of inactivation are defined by the organ's developmental status. These results have important implications for clinical understanding of the disease and therapeutic approaches.


description_brief: Genes up-regulated at the peak of an antigen response of naive CD8+ [GeneID=925;926] T-cells.
systematic_name: M11884
exact_source: Table 1S
source_species_code: MM
GEO_id: GSE1921
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Naive T cells proliferate independently of cognate antigen when introduced into lymphopenic hosts. Lymphopenia-induced proliferation depends on low-affinity MHC/self-peptide complexes and on IL-7. To elucidate the intracellular signals mediating this proliferation, we analyzed changes in gene expression in naive CD8+ T cells at different times after their transfer into a lymphopenic environment. The genes induced in response to lymphopenia were largely an attenuated subset of those turned up by full antigenic stimulation, including genes related to cell cycling, whereas excluding genes specifically associated with effector activity. After the initial phase of proliferation in an empty compartment, the naive T cells adopted a stable pattern of gene expression similar to that of antigen-experienced memory cells. Thus, T cells proliferating in lymphopenic hosts do not exhibit a unique gene-expression profile, instead relying on traditional signals for this antigen-independent proliferation; this process ultimately results in differentiation to authentic memory cells.


systematic_name: M19469
exact_source: Suppl. data file 'BMT_356_public.xls': A7 vs S7 P<.01 and FC<0.5
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Hepatic graft versus host disease (GVHD), day 7: down-regulated in allogeneic vs syngeneic bone marrow transplant.

description_full:
  The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon gamma (IFN-gamma)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-gamma protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-gamma early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.


systematic_name: M13337
exact_source: Suppl. data file 'BMT_356_public.xls': A35 vs S35 P<.01 and FC<0.5
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Hepatic graft versus host disease (GVHD), day 35: genes down-regulated in allogeneic vs syngeneic bone marrow transplant.

description_full:
[cell repeats an earlier one in this file: 1321 characters]


description_brief: Genes down-regulated in fibroblasts from MLL [GeneID=4297] knockout mice.
systematic_name: M1904
exact_source: Table 2
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  The human mixed lineage leukemia (MLL) gene is involved in about 50 different chromosomal translocations, associated with the disease phenotype of acute leukemia. However, the normal function of MLL is less understood. Homozygous knockouts of murine Mll were embryonal lethal, while heterozygous disruption led to aberrant hox gene expression associated with skeletal malformations, growth retardation, and impaired hematopoiesis. To understand MLL functions on the molecular level, gene expression profiling experiments were performed with a pair of murine cell lines (MLL(+/+) and MLL(-/-)). Microarray hybridization experiments revealed 197 potential target genes that are differentially expressed, providing new and important clues about MLL functions.


description_brief: Genes up-regulated during differentiation from large pre-BII to small pre-BII lymphocyte.
systematic_name: M5588
exact_source: Table 2S: CHGF_LAR_SMA>=4
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Gene expression profiles of five consecutive stages of mouse B cell development were generated with high-density oligonucleotide arrays from as few as 2 x 10(4) ex vivo isolated and flow-cytometrically purified cells. Between 2.8% and 6.8% of all genes change on differentiation from one cellular stage to the next by at least twofold. The entire pathway involves differential expression of 10.7% of all genes. Previously known expression patterns of 15 genes (like surrogate light chain, RAG-1/2, MHC class II, mel-14 antigen) are confirmed. The gene expression patterns of the proliferating pre-BI and large pre-BII cells on the one hand, and the resting immature and mature B cells on the other hand, are most similar to each other. Small pre-BII cells display a pattern that is transitional between these two groups. Most of the genes expressed in early precursors are involved in general processes, like protein folding or cell cycle regulation, whereas more mature precursors express genes involved in more specific molecular programs (cell surface receptors, secreted factors, and adhesion molecules, among others). Between 19 and 139 genes share a given expression pattern. Combining knowledge about gene function and expression pattern allows identification of novel candidate genes potentially involved in self-maintenance of pre-BI cells, allelic exclusion and pre-B cell receptor signaling in large pre BII cells, cell-cycle arrest of small pre-BII cells, propensity toward apoptosis or anergization in immature B cells, propensity toward cell division and activation in mature B cells, and stage-specific interactions with stromal cells in the bone marrow.


systematic_name: M1927
exact_source: Fig. 1: DOWN in partially reprogrammed iPS/ES
source_species_code: MM
GEO_id: GSE10871
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in partially reprogrammed and pluripotent cell populations (induced, iPS; and embryonic stem cells, ES) compared to parental lineage-commited cell lines.

description_full:
  Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.


systematic_name: M1928
exact_source: Fig. 1: UP in partially reprogrammed cells
source_species_code: MM
GEO_id: GSE10781
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in cells that have been partially reprogrammed to pluripotency: comparison with the parental lineage-committed cell lines, fully reprogrammed stem cells, and embryonic stem cells.

description_full:
  Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.


systematic_name: M1944
exact_source: Fig. 7B: Genes decreased by Mad1
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated by overexpression of MAD1 [GeneID=4084] in primary thymocytes from RAG2 [GeneID=5897] knockout mice.

description_full:
  Activated lymphocytes must increase in size and duplicate their contents (cell growth) before they can divide. The molecular events that control cell growth in proliferating lymphocytes and other metazoan cells are still unclear. Here, we utilized transgenesis to provide evidence suggesting that the basic helix-loop- helix-zipper (bHLHZ) transcriptional repressor Mad1, considered to be an antagonist of Myc function, inhibits lymphocyte expansion, maturation and growth following pre-T-cell receptor (pre-TCR) and TCR stimulation. Furthermore, we utilized cDNA microarray technology to determine that, of the genes repressed by Mad1, the majority (77%) are involved in cell growth, which correlates with a decrease in size of Mad1 transgenic thymocytes. Over 80% of the genes repressed by Mad1 have previously been found to be induced by Myc. These results suggest that a balance between Myc and Mad levels may normally modulate lymphocyte proliferation and development in part by controlling expression of growth-regulating genes.


systematic_name: M1945
exact_source: Table 2
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MEF cells (embryonic fibroblast) after expression of E2F1 or E2F2 [GeneID=1869;1870].

description_full:
  We have used high-density DNA microarrays to provide an analysis of gene regulation during the mammalian cell cycle and the role of E2F in this process. Cell cycle analysis was facilitated by a combined examination of gene control in serum-stimulated fibroblasts and cells synchronized at G(1)/S by hydroxyurea block that were then released to proceed through the cell cycle. The latter approach (G(1)/S synchronization) is critical for rigorously maintaining cell synchrony for unambiguous analysis of gene regulation in later stages of the cell cycle. Analysis of these samples identified seven distinct clusters of genes that exhibit unique patterns of expression. Genes tend to cluster within these groups based on common function and the time during the cell cycle that the activity is required. Placed in this context, the analysis of genes induced by E2F proteins identified genes or expressed sequence tags not previously described as regulated by E2F proteins; surprisingly, many of these encode proteins known to function during mitosis. A comparison of the E2F-induced genes with the patterns of cell growth-regulated gene expression revealed that virtually all of the E2F-induced genes are found in only two of the cell cycle clusters; one group was regulated at G(1)/S, and the second group, which included the mitotic activities, was regulated at G(2). The activation of the G(2) genes suggests a broader role for E2F in the control of both DNA replication and mitotic activities.


systematic_name: M1967
exact_source: Table 2S: Promoter=HCP & MCV8.1=K27
source_species_code: MM
GEO_id: GSE11074
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes with high-CpG-density promoters (HCP) bearing the tri-methylation mark at H3K27 (H3K27me3) in MCV8.1 (induced pluripotent cells, iPS).

description_full:
  Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.


systematic_name: M1968
exact_source: Table 2S: Promoter=HCP & MCV8.1=none
source_species_code: MM
GEO_id: GSE11074
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes with high-CpG-density promoters (HCP) without H3 methylation marks at either H3K4 or H3K27 in MCV8.1 cells (induced pluripotent cells, iPS).

description_full:
[cell repeats an earlier one in this file: 1366 characters]


description_brief: Genes whose over-expression is associated with the risk of death in multiple cancer types
systematic_name: M13007
exact_source: Table 3, 2S
source_species_code: MM
contributor: Yujin Hoshida
contrib_organization: Broad Institute
description_full:
  Activation in transformed cells of normal stem cells' self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene-driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell-resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell-like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1-driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.


systematic_name: M1977
exact_source: Fig. S7: AML1, red
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in CD4+ [GeneID=920] T lymphocytes by expression of AML1 [GeneID=861] off a viral vector.

description_full:
  Naturally arising CD25+CD4+ regulatory T cells (T(R) cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy. T(R) cells specifically express the transcription factor Foxp3, a key regulator of T(R)-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and upregulate T(R)-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development, activates IL-2 and IFN-gamma gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural T(R) cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN-gamma production, upregulates T(R)-cell-associated molecules, and exerts suppressive activity. This transcriptional control of T(R)-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.


systematic_name: M1978
exact_source: Fig. S7: AML1, green
source_species_code: MM
contributor: Jessica Robertson
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in CD4+ [GeneID=920] T lymphocytes by expression of AML1 [GeneID=861] off a viral vector.

description_full:
  Naturally arising CD25+CD4+ regulatory T cells (T(R) cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy. T(R) cells specifically express the transcription factor Foxp3, a key regulator of T(R)-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and upregulate T(R)-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development, activates IL-2 and IFN-gamma gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural T(R) cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN-gamma production, upregulates T(R)-cell-associated molecules, and exerts suppressive activity. This transcriptional control of T(R)-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.


systematic_name: M1989
exact_source: Evasion > 1 & Tolerogenic < 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Selected genes with immunologic function which were reciprocally changed in evasion and tolerogenic tumor models.

description_full:
  We have previously shown T-cell-mediated rejection of the neu-overexpressing mammary carcinoma cells (MMC) in wild-type FVB mice. However, following rejection of primary tumors, a fraction of animals experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (tumor evasion model) after a long latency period. In the present study, we determined that T cells derived from wild-type FVB mice can specifically recognize MMC by secreting IFN-gamma and can induce apoptosis of MMC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors and cannot reject it (tumor tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC tumors, we compared transcriptional patterns within the tumor microenvironment of MMC undergoing rejection with those that resisted it either because of tumor evasion/antigen loss recurrence (ANV tumors) or because of intrinsic tolerance mechanisms displayed by the transgenic mice. Gene profiling confirmed that immune rejection is primarily mediated through activation of IFN-stimulated genes and T-cell effector mechanisms. The tumor evasion model showed combined activation of Th1 and Th2 with a deviation toward Th2 and humoral immune responses that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials.


systematic_name: M6175
exact_source: Table 13S: Early/Late Ratio < 0.8
source_species_code: MM
GEO_id: E-MEXP-1853,E-MEXP-1851,E-MEXP-1852
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated at early fetal liver stage (embryonic days  E11.5 - E12.5) compared to the late fetal liver stage (embryonic days E14.5 - E16.5).

description_full:
[cell repeats an earlier one in this file: 854 characters]


systematic_name: M2000
exact_source: Table 4S: Class=HCP & ESC state=K27
source_species_code: MM
GEO_id: GSE12241
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with high-CpG-density promoters (HCP) bearing histone H3 K27 trimethylation mark (H327me3) in embryonic stem cells (ES).

description_full:
  We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.


systematic_name: M2002
exact_source: Table 4S: Class=HCP & ESC state=None
source_species_code: MM
GEO_id: GSE12241
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with high-CpG-density promoters (HCP) without H3 methylation marks at K4 and K27 in embryonic stem cells (ES).

description_full:
  We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.


systematic_name: M2020
exact_source: Table 4S: Class=HCP & MEF state=None
source_species_code: MM
GEO_id: GSE12241
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with high-CpG-density promoters (HCP) with unmethylated histone H3 in MEF cells (embryonic fibroblast).

description_full:
  We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.


systematic_name: M16708
exact_source: Supp. data: out_b_data Web S6: Cluster No.=5
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 5.

description_full:
  Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression. At the time of implantation, Hoxa-10 mediates the progesterone-stimulated proliferation of uterine stromal cells. Hoxa-10 mutants express a stromal cell proliferation defect that is accompanied by quantitative or spatial alterations in the expression of two cyclin-dependent kinase inhibitor genes, p57 and p15. Hoxa-10 deficiency also leads to a severe local immunological disturbance, characterized by a polyclonal proliferation of T cells, that occurs in place of the normal progesterone-mediated immunosuppression in the periimplantation uterus.


systematic_name: M18153
exact_source: Supp. data: out_b_data Web S6: Cluster No.=9
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 9.

description_full:
  Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression. At the time of implantation, Hoxa-10 mediates the progesterone-stimulated proliferation of uterine stromal cells. Hoxa-10 mutants express a stromal cell proliferation defect that is accompanied by quantitative or spatial alterations in the expression of two cyclin-dependent kinase inhibitor genes, p57 and p15. Hoxa-10 deficiency also leads to a severe local immunological disturbance, characterized by a polyclonal proliferation of T cells, that occurs in place of the normal progesterone-mediated immunosuppression in the periimplantation uterus.


systematic_name: M1033
exact_source: Supp. data: out_b_data Web S6: Cluster No.=10
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 10.

description_full:
  Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression. At the time of implantation, Hoxa-10 mediates the progesterone-stimulated proliferation of uterine stromal cells. Hoxa-10 mutants express a stromal cell proliferation defect that is accompanied by quantitative or spatial alterations in the expression of two cyclin-dependent kinase inhibitor genes, p57 and p15. Hoxa-10 deficiency also leads to a severe local immunological disturbance, characterized by a polyclonal proliferation of T cells, that occurs in place of the normal progesterone-mediated immunosuppression in the periimplantation uterus.


systematic_name: M19360
exact_source: Supp. data: out_b_data Web S6: Cluster No.=11
source_species_code: MM
GEO_id: GSE106,GSE107
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 11.

description_full:
[cell repeats an earlier one in this file: 952 characters]


systematic_name: M13713
exact_source: Supp. data: out_b_data Web S6: Cluster No.=13
source_species_code: MM
GEO_id: GSE106,GSE107
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 13.

description_full:
[cell repeats an earlier one in this file: 952 characters]


systematic_name: M8751
exact_source: Supp. data: out_b_data Web S6: Cluster No.=14
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 14.

description_full:
[cell repeats an earlier one in this file: 952 characters]


systematic_name: M2687
exact_source: Supp. data: out_b_data Web S6: Cluster No.=15
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 15.

description_full:
[cell repeats an earlier one in this file: 952 characters]


systematic_name: M18400
exact_source: Supp. data: out_b_data Web S6: Cluster No.=16
source_species_code: MM
GEO_id: GSE107,GSE106
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 16.

description_full:
[cell repeats an earlier one in this file: 952 characters]


systematic_name: M2336
exact_source: Supp. data: out_b_data Web S6: Cluster No.=17
source_species_code: MM
GEO_id: GSE106,GSE107
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes co-regulated in uterus during a time course response to progesterone [PubChem=5994]: SOM cluster 17.

description_full:
[cell repeats an earlier one in this file: 952 characters]


description_brief: Genes up-regulated in pyloric atrium with knockout of TFF2 [GeneID=7032].
systematic_name: M2035
exact_source: Fig. 2: red
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  BACKGROUND AND AIMS: The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. METHODS: TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. RESULTS: On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach.


systematic_name: M2056
exact_source: Table 1: Fold-TGZ =< -1.1
source_species_code: HS
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Adipocyte abundant genes down-regulated in 3T3-L1 cells (fibroblasts induced to differentiate to adipocytes) in response to troglitazone [PubChem=5591].

description_full:
[cell repeats an earlier one in this file: 2017 characters]


systematic_name: M2080
exact_source: Fig. 1S: red in WT
source_species_code: MM
GEO_id: GSE1742
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated by TGFB1 [GeneID=7040] in MEF cells (embryonic fibroblast) via TGFB1R [GeneID=7046].

description_full:
  Transforming growth factor-beta1 (TGF-beta) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-beta binds to receptor complexes consisting of TGF-beta receptor type II (TbetaRII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of TbetaRII/Alk5 can be relevant for TGF-beta signaling. We have screened for alternative receptors for TGF-beta and also for gene targets of TGF-beta signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-beta-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-beta. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-beta-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-beta signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.


description_brief: Genes up-regulated by hypoxia in TRAMP-C cells (prostatic cancer).
systematic_name: M2133
exact_source: Table 2S
source_species_code: MM
GEO_id: GSE18478
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the TRAMP mouse model was suppressed in mice lacking the ubiquitin ligase Siah2, which regulates HIF-1alpha availability. Cooperation between HIF-1alpha and FoxA2, a transcription factor expressed in NE tissue, promotes recruitment of p300 to transactivate select HIF-regulated genes, Hes6, Sox9, and Jmjd1a. These HIF-regulated genes are highly expressed in metastatic PCa and required for hypoxia-mediated NE phenotype, metastasis in PCa, and the formation of NE tumors. Tissue-specific expression of FoxA2 combined with Siah2-dependent HIF-1alpha availability enables a transcriptional program required for NE prostate tumor development and NE phenotype in PCa.


systematic_name: M2182
exact_source: Table 1AS
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Classic adipogenic genes (group 1) that are induced by PPARG  [GeneID=5468] during adipogenesis in 3T3-L1 preadipocytes.

description_full:
  Peroxisome proliferator-activated receptor gamma (PPARgamma) activity is regulated through association with ligands that include the thiazolidinedione class of antidiabetic drugs, as well as derivatives of polyunsaturated fatty acids. Induction of PPARgamma target gene expression involves ligand-dependent reconfiguration of the ligand-binding domain (LBD), followed by recruitment of specific transcriptional coactivators. In this study, we have identified an amino acid (F372) within helix 7 of the LBD that is required for the response of PPARgamma to endogenous ligands. Additionally, the data show that this amino acid is also required for expression of a novel subset of adipocyte genes (group 2), including fibroblast growth factor 21 (FGF21), and that the FGF21 gene is a direct target of PPARgamma. Expression of the group 2 genes is selectively repressed by the NAD-dependent deacetylase SIRT1 in mature 3T3-L1 adipocytes, since knockdown of SIRT1 through the constitutive expression of a corresponding RNA interference enhances their expression without affecting the expression of classic adipogenic genes, such as adiponectin and FABP4/aP2. It appears that many of the group 2 genes repressed by SIRT1 in mature adipocytes correspond to the same set of genes that are selectively activated by treatment of fat cells with the PPARgamma ligand, troglitazone. These data support a role for helix 7 of the LBD of PPARgamma in regulating adipocyte function and suggest that inhibition of SIRT1 in adipocytes induces the same insulin-sensitizing action as PPARgamma ligands.


systematic_name: M2183
exact_source: Table 1BS
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Adipogenic genes (group 2) that are selectively repressed by  SIRT1 [GeneID=23411] in mature 3T3-L1 adipocytes.

description_full:
  Peroxisome proliferator-activated receptor gamma (PPARgamma) activity is regulated through association with ligands that include the thiazolidinedione class of antidiabetic drugs, as well as derivatives of polyunsaturated fatty acids. Induction of PPARgamma target gene expression involves ligand-dependent reconfiguration of the ligand-binding domain (LBD), followed by recruitment of specific transcriptional coactivators. In this study, we have identified an amino acid (F372) within helix 7 of the LBD that is required for the response of PPARgamma to endogenous ligands. Additionally, the data show that this amino acid is also required for expression of a novel subset of adipocyte genes (group 2), including fibroblast growth factor 21 (FGF21), and that the FGF21 gene is a direct target of PPARgamma. Expression of the group 2 genes is selectively repressed by the NAD-dependent deacetylase SIRT1 in mature 3T3-L1 adipocytes, since knockdown of SIRT1 through the constitutive expression of a corresponding RNA interference enhances their expression without affecting the expression of classic adipogenic genes, such as adiponectin and FABP4/aP2. It appears that many of the group 2 genes repressed by SIRT1 in mature adipocytes correspond to the same set of genes that are selectively activated by treatment of fat cells with the PPARgamma ligand, troglitazone. These data support a role for helix 7 of the LBD of PPARgamma in regulating adipocyte function and suggest that inhibition of SIRT1 in adipocytes induces the same insulin-sensitizing action as PPARgamma ligands.


description_brief: Genes up-regulated in placenta of mice with EHMT2 [GeneID=10919] knocked out.
systematic_name: M2189
exact_source: Table 1AS: SLR > 0
source_species_code: MM
GEO_id: GSE7674
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET domain protein G9a. We found that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression was unchanged at the domains analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is impaired in the absence of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3. These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast.


description_brief: Genes down-regulated in liver samples of liver-specific knockout of HNF4A [GeneID=3172].
systematic_name: M2194
exact_source: Table 2S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.


systematic_name: M2206
exact_source: Fig. 3S: fold change < 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in immature bone marrow progenitor cells upon knock out of CBFA2T3 [GeneID=863].

description_full:
  While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only a limited number of transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here, we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is required for hematopoietic progenitor cell fate decisions and for early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells toward the granulocytic/macrophage lineage while reducing the numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of Mtg16 impaired the rapid expansion of short-term stem cells, multipotent progenitor cells, and megakaryocyte-erythroid progenitor cells that is required under hematopoietic stress/emergency. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16(-/-) defect.


description_brief: Genes up-regulated in RAW 264.7 cells (macrophage) upon stimulation with TNFSF11 [GeneID=8600].
systematic_name: M2207
exact_source: Table 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jagged1 and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective gamma-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATc1 promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-kappaB pathways that is relevant in osteoclastogenesis.


systematic_name: M2223
exact_source: Table 2S: Fold > 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in osteoblasts from wild type male mice compared to those with AR [GeneID=367] knockout.

description_full:
  While androgen receptor (AR)-deficient mice developed osteopenia in endochondral bones due to the high bone turnover with increased bone resorption by osteoclasts, little is known about the mechanism of intramembranous bone loss contributed by AR in osteoblasts. Here, we discovered a dramatic decrease in the area of calcification, new bone, and the number of osteocytes in calvaria from AR-deficient mice related to a reduction in mineralization caused, in part, by the diminished activity of AR-deficient osteoblasts. Enforced AR expression in differentiated osteoblasts boosts mineralization while knockdown of AR expression prevents androgen-induced mineralization. We identified the tissue-nonspecific alkaline phosphatase (TNSALP) and several members of small integrin binding ligand N-linked glycoprotein (SIBLING) gene family as androgen target genes required for AR-mediated bone formation. We show that inorganic phosphate (P(i)) levels and TNSALP activity increased in response to androgen/AR and P(i) signals increase the expression and translocation of AR. The ectopic expression of TNSALP or P(i) partially rescued the bone loss due to AR deficiency. Thus, androgen/AR signaling plays an essential role in bone formation by coordinating the expression of genes associated with phosphate regulation.


description_brief: Genes up-regulated during adipogenesis of 3T3-L1 cells (fibroblast).
systematic_name: M2270
exact_source: Fig. 5: mRNA arrow(s) up
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  The histone H3 lysine 79 methyltransferase DOT1L/KMT4 can promote an oncogenic pattern of gene expression through binding with several MLL fusion partners found in acute leukemia. However, the normal function of DOT1L in mammalian gene regulation is poorly understood. Here we report that DOT1L recruitment is ubiquitously coupled with active transcription in diverse mammalian cell types. DOT1L preferentially occupies the proximal transcribed region of active genes, correlating with enrichment of H3K79 di- and trimethylation. Furthermore, Dot1l mutant fibroblasts lacked H3K79 di- and trimethylation at all sites examined, indicating that DOT1L is the sole enzyme responsible for these marks. Importantly, we identified chromatin immunoprecipitation (ChIP) assay conditions necessary for reliable H3K79 methylation detection. ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. We also observed enrichment of H3K79 monomethylation at intergenic regions occupied by DNA-binding transcriptional activators. Our findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin, suggesting a widespread mechanism for parallel or sequential recruitment of DOT1L and MLL to genes in their normal on state.


systematic_name: M2298
exact_source: Table 1S: Comparison=9.5 dpc KO versus 8.5 dpc and 9.5 dpc WT
source_species_code: MM
GEO_id: E-MEXP-832
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in 9.5 days post coitus (dpc) embryos with COMMD1 [GeneID=150684] knockout compared to normal 8.5 dpc and 9.5 dpc embryos.

description_full:
  COMMD1 (previously known as MURR1) belongs to a novel family of proteins termed the copper metabolism gene MURR1 domain (COMMD) family. The 10 COMMD family members are well conserved between vertebrates, but the functions of most of the COMMD proteins are unknown. We recently established that COMMD1 is associated with the hepatic copper overload disorder copper toxicosis in Bedlington terriers. Recent in vitro studies indicate that COMMD1 has multiple functions, including sodium transport and NF-kappaB signaling. To elucidate the function of Commd1 in vivo, we generated homozygous Commd1 null (Commd1(-/-)) mice. Commd1(-/-) embryos died in utero between 9.5 and 10.5 days postcoitum (dpc), their development was generally retarded, and placenta vascularization was absent. Microarray analysis identified transcriptional upregulation of hypoxia-inducible factor 1 (HIF-1) target genes in 9.5-dpc Commd1(-/-) embryos compared to normal embryos, a feature that was associated with increased Hif-1alpha stability. Consistent with these observations, COMMD1 physically associates with HIF-1alpha and inhibits HIF-1alpha stability and HIF-1 transactivation in vitro. Thus, this study identifies COMMD1 as a novel regulator of HIF-1 activity and shows that Commd1 deficiency in mice leads to embryonic lethality associated with dysregulated placenta vascularization.


systematic_name: M2299
exact_source: Table 1S: Comparison=9.5 dpc KO versus 9.5 dpc WT
source_species_code: MM
GEO_id: E-MEXP-832
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in 9.5 days post coitus (dpc) embryos with COMMD1 [GeneID=150684] knockout compared to normal 9.5 dpc embryos.

description_full:
  COMMD1 (previously known as MURR1) belongs to a novel family of proteins termed the copper metabolism gene MURR1 domain (COMMD) family. The 10 COMMD family members are well conserved between vertebrates, but the functions of most of the COMMD proteins are unknown. We recently established that COMMD1 is associated with the hepatic copper overload disorder copper toxicosis in Bedlington terriers. Recent in vitro studies indicate that COMMD1 has multiple functions, including sodium transport and NF-kappaB signaling. To elucidate the function of Commd1 in vivo, we generated homozygous Commd1 null (Commd1(-/-)) mice. Commd1(-/-) embryos died in utero between 9.5 and 10.5 days postcoitum (dpc), their development was generally retarded, and placenta vascularization was absent. Microarray analysis identified transcriptional upregulation of hypoxia-inducible factor 1 (HIF-1) target genes in 9.5-dpc Commd1(-/-) embryos compared to normal embryos, a feature that was associated with increased Hif-1alpha stability. Consistent with these observations, COMMD1 physically associates with HIF-1alpha and inhibits HIF-1alpha stability and HIF-1 transactivation in vitro. Thus, this study identifies COMMD1 as a novel regulator of HIF-1 activity and shows that Commd1 deficiency in mice leads to embryonic lethality associated with dysregulated placenta vascularization.


systematic_name: M2302
exact_source: Table 6S-7S: Comparison=9.5 dpc KO and 8.5 dpc WT versus 9.5 dpc WT
source_species_code: MM
GEO_id: E-MEXP-832
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes down-regulated in 9.5 days post coitus (dpc) embryos with COMMD1 [GeneID=150684] knockout and in normal 8.5 dpc embryos compared to normal 9.5 dpc embryos.

description_full:
  COMMD1 (previously known as MURR1) belongs to a novel family of proteins termed the copper metabolism gene MURR1 domain (COMMD) family. The 10 COMMD family members are well conserved between vertebrates, but the functions of most of the COMMD proteins are unknown. We recently established that COMMD1 is associated with the hepatic copper overload disorder copper toxicosis in Bedlington terriers. Recent in vitro studies indicate that COMMD1 has multiple functions, including sodium transport and NF-kappaB signaling. To elucidate the function of Commd1 in vivo, we generated homozygous Commd1 null (Commd1(-/-)) mice. Commd1(-/-) embryos died in utero between 9.5 and 10.5 days postcoitum (dpc), their development was generally retarded, and placenta vascularization was absent. Microarray analysis identified transcriptional upregulation of hypoxia-inducible factor 1 (HIF-1) target genes in 9.5-dpc Commd1(-/-) embryos compared to normal embryos, a feature that was associated with increased Hif-1alpha stability. Consistent with these observations, COMMD1 physically associates with HIF-1alpha and inhibits HIF-1alpha stability and HIF-1 transactivation in vitro. Thus, this study identifies COMMD1 as a novel regulator of HIF-1 activity and shows that Commd1 deficiency in mice leads to embryonic lethality associated with dysregulated placenta vascularization.


systematic_name: M2307
exact_source: Table 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Representative genes up-regulated in C2C12 cells (myoblast) lacking NFkB activity due to expression of a super repressor form of NFKBIA [GeneID=4792].

description_full:
  NF-kappaB signaling is implicated as an important regulator of skeletal muscle homeostasis, but the mechanisms by which this transcription factor contributes to muscle maturation and turnover remain unclear. To gain insight into these mechanisms, gene expression profiling was examined in C2C12 myoblasts devoid of NF-kappaB activity. Interestingly, even in proliferating myoblasts, the absence of NF-kappaB caused the pronounced induction of several myofibrillar genes, suggesting that NF-kappaB functions as a negative regulator of late-stage muscle differentiation. Although several myofibrillar promoters contain predicted NF-kappaB binding sites, functional analysis using the troponin-I2 gene as a model revealed that NF-kappaB-mediated repression does not occur through direct DNA binding. In the search for an indirect mediator, the transcriptional repressor YinYang1 (YY1) was identified. While inducers of NF-kappaB stimulated YY1 expression in multiple cell types, genetic ablation of the RelA/p65 subunit of NF-kappaB in both cultured cells and adult skeletal muscle correlated with reduced YY1 transcripts and protein. NF-kappaB regulation of YY1 occurred at the transcriptional level, mediated by direct binding of the p50/p65 heterodimer complex to the YY1 promoter. Furthermore, YY1 was found associated with multiple myofibrillar promoters in C2C12 myoblasts containing NF-kappaB activity. Based on these results, we propose that NF-kappaB regulation of YY1 and transcriptional silencing of myofibrillar genes represent a new mechanism by which NF-kappaB functions in myoblasts to modulate skeletal muscle differentiation.


systematic_name: M2327
exact_source: Table 1S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes translationally regulated in MEF cells (embryonic fibroblasts) in response to serum starvation but not by rapamycin (sirolimus) [PubChem=6610346].

description_full:
  The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1). However, how TSC1 and TSC2 control overall protein synthesis and the translation of specific mRNAs in response to different mitogenic and nutritional stimuli is largely unknown. We show here that serum withdrawal inhibits mTORC1 signaling, causes disassembly of translation initiation complexes, and causes mRNA redistribution from polysomes to subpolysomes in wild-type mouse embryo fibroblasts (MEFs). In contrast, these responses are defective in Tsc1(-/-) or Tsc2(-/-) MEFs. Microarray analysis of polysome- and subpolysome-associated mRNAs uncovered specific mRNAs that are translationally regulated by serum, 90% of which are TSC1 and TSC2 dependent. Surprisingly, the mTORC1 inhibitor, rapamycin, abolished mTORC1 activity but only affected approximately 40% of the serum-regulated mRNAs. Serum-dependent signaling through mTORC1 and polysome redistribution of global and individual mRNAs were restored upon re-expression of TSC1 and TSC2. Serum-responsive mRNAs that are sensitive to inhibition by rapamycin are highly enriched for terminal oligopyrimidine and for very short 5' and 3' untranslated regions. These data demonstrate that the TSC1/TSC2 complex regulates protein translation through mainly mTORC1-dependent mechanisms and implicates a discrete profile of deregulated mRNA translation in tuberous sclerosis pathology.


systematic_name: M2328
exact_source: Table 2S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes translationally regulated in MEF cells (embryonic fibroblasts) in response to serum starvation and by rapamycin (sirolimus) [PubChem=6610346].

description_full:
  The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1). However, how TSC1 and TSC2 control overall protein synthesis and the translation of specific mRNAs in response to different mitogenic and nutritional stimuli is largely unknown. We show here that serum withdrawal inhibits mTORC1 signaling, causes disassembly of translation initiation complexes, and causes mRNA redistribution from polysomes to subpolysomes in wild-type mouse embryo fibroblasts (MEFs). In contrast, these responses are defective in Tsc1(-/-) or Tsc2(-/-) MEFs. Microarray analysis of polysome- and subpolysome-associated mRNAs uncovered specific mRNAs that are translationally regulated by serum, 90% of which are TSC1 and TSC2 dependent. Surprisingly, the mTORC1 inhibitor, rapamycin, abolished mTORC1 activity but only affected approximately 40% of the serum-regulated mRNAs. Serum-dependent signaling through mTORC1 and polysome redistribution of global and individual mRNAs were restored upon re-expression of TSC1 and TSC2. Serum-responsive mRNAs that are sensitive to inhibition by rapamycin are highly enriched for terminal oligopyrimidine and for very short 5' and 3' untranslated regions. These data demonstrate that the TSC1/TSC2 complex regulates protein translation through mainly mTORC1-dependent mechanisms and implicates a discrete profile of deregulated mRNA translation in tuberous sclerosis pathology.


systematic_name: M2329
exact_source: Table 3S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes translationally regulated in MEF cells (embryonic fibroblasts) by rapamycin (sirolimus) [PubChem=6610346] but not in response to serum deprivation.

description_full:
  The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1). However, how TSC1 and TSC2 control overall protein synthesis and the translation of specific mRNAs in response to different mitogenic and nutritional stimuli is largely unknown. We show here that serum withdrawal inhibits mTORC1 signaling, causes disassembly of translation initiation complexes, and causes mRNA redistribution from polysomes to subpolysomes in wild-type mouse embryo fibroblasts (MEFs). In contrast, these responses are defective in Tsc1(-/-) or Tsc2(-/-) MEFs. Microarray analysis of polysome- and subpolysome-associated mRNAs uncovered specific mRNAs that are translationally regulated by serum, 90% of which are TSC1 and TSC2 dependent. Surprisingly, the mTORC1 inhibitor, rapamycin, abolished mTORC1 activity but only affected approximately 40% of the serum-regulated mRNAs. Serum-dependent signaling through mTORC1 and polysome redistribution of global and individual mRNAs were restored upon re-expression of TSC1 and TSC2. Serum-responsive mRNAs that are sensitive to inhibition by rapamycin are highly enriched for terminal oligopyrimidine and for very short 5' and 3' untranslated regions. These data demonstrate that the TSC1/TSC2 complex regulates protein translation through mainly mTORC1-dependent mechanisms and implicates a discrete profile of deregulated mRNA translation in tuberous sclerosis pathology.


systematic_name: M2331
exact_source: Table 4S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes translationally repressed by rapamycin (sirolimus) [PubChem=6610346] in MEF cells (embryonic fibroblast) lacking either TSC1 or TSC2 [GeneID=7248, 7249] but not in the wild type cells.

description_full:
[cell repeats an earlier one in this file: 1522 characters]


systematic_name: M2334
exact_source: Table 5S: genes 1-39 (second list)
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes translationally up-regulated by serum in MEF cells (embryonic fibroblast) lacking TSC2 [GeneID=7249].

description_full:
[cell repeats an earlier one in this file: 1522 characters]


systematic_name: M2368
exact_source: Suppl. file 1: cluster 5
source_species_code: MM
GEO_id: GSE14406
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated during later stage of differentiation of Oli-Neu cells (oligodendroglial precursor) in response to PD174265 [PubChem=4709].

description_full:
  Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a critical role in oligodendrocyte differentiation, we performed time-dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into process-forming and myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the completely differentiated state, where regulated gene sets overlap maximally. In order to also gain insight into the functional role of genes that are regulated in this process, we silenced 88 of these genes using small interfering RNA and identified multiple repressors of spontaneous differentiation of Oli-neu, most of which were confirmed in rat primary oligodendrocyte precursors cells. Among these repressors were CNP, a well-known myelin constituent, and three phosphatases, each known to negatively control mitogen-activated protein kinase cascades. We show that a novel inhibitor for one of the identified genes, dual-specificity phosphatase DUSP10/MKP5, was also capable of inducing oligodendrocyte differentiation in primary oligodendrocyte precursors. Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition.


description_brief: Genes up-regulated in E12.5 forelimb buds with POR [GeneID=5447] knockout.
systematic_name: M2383
exact_source: Fig. 7C: Fold change > 1
source_species_code: MM
GEO_id: E-TABM-367
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for all microsomal cytochrome P450 enzymes, which catalyze the metabolism of a wide spectrum of xenobiotic and endobiotic compounds. Point mutations in POR have been found recently in patients with Antley-Bixler-like syndrome, which includes limb skeletal defects. In order to study P450 function during limb and skeletal development, we deleted POR specifically in mouse limb bud mesenchyme. Forelimbs and hind limbs in conditional knockout (CKO) mice were short with thin skeletal elements and fused joints. POR deletion occurred earlier in forelimbs than in hind limbs, leading additionally to soft tissue syndactyly and loss of wrist elements and phalanges due to changes in growth, cell death, and skeletal segmentation. Transcriptional analysis of E12.5 mouse forelimb buds demonstrated the expression of P450s involved in retinoic acid, cholesterol, and arachidonic acid metabolism. Biochemical analysis of CKO limbs confirmed retinoic acid excess. In CKO limbs, expression of genes throughout the whole cholesterol biosynthetic pathway was upregulated, and cholesterol deficiency can explain most aspects of the phenotype. Thus, cellular POR-dependent cholesterol synthesis is essential during limb and skeletal development. Modulation of P450 activity could contribute to susceptibility of the embryo and developing organs to teratogenesis.


description_brief: Genes differentially expressed in ES cells with DPPA4 [GeneID=55211] knockout.
systematic_name: M2399
exact_source: Table 1S
source_species_code: MM
GEO_id: GSE15173
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Dppa4 (developmental pluripotency-associated 4) has been identified in several high-profile screens as a gene that is expressed exclusively in pluripotent cells. It encodes a nuclear protein with an SAP-like domain and appears to be associated preferentially with transcriptionally active chromatin. Its exquisite expression pattern and results of RNA interference experiments have led to speculation that Dppa4, as well as its nearby homolog Dppa2, might play essential roles in embryonic stem (ES) cell function and/or germ cell development. To rigorously assess suggested roles, we have generated Dppa4-deficient and Dppa4/Dppa2 doubly deficient ES cells, as well as mice lacking Dppa4. Contrary to predictions, we find that Dppa4 is completely dispensable for ES cell identity and germ cell development. Instead, loss of Dppa4 in mice results in late embryonic/perinatal death and striking skeletal defects with partial penetrance. Thus, surprisingly, Dppa4-deficiency affects tissues that apparently never transcribed the gene, and at least some loss-of-function defects manifest phenotypically at an embryonic stage long after physiologic Dppa4 expression has ceased. Concomitant with targeted gene inactivation, we have introduced into the Dppa4 locus a red fluorescent marker (tandem-dimer red fluorescent protein) that is compatible with green fluorescent proteins and allows noninvasive visualization of pluripotent cells and reprogramming events.


systematic_name: M2415
exact_source: Table 1S_1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters bound by both PPARG and RXRA [GeneID=5468, 6256] at 36 h time point of adipocyte differentiation of 3T3-L1 cells (preadipocyte).

description_full:
  Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR gamma during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR gamma and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR gamma transcriptional activity leads to the induction of H4K20me1 modification of PPAR gamma and its targets and thereby promotes adipogenesis. We also show that PPAR gamma targets PPAR gamma2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.


systematic_name: M2416
exact_source: Table 1S_2
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters bound by PPARG [GeneID=5468] at 36 h time point of adipocyte differentiation of 3T3-L1 cells (preadipocyte).

description_full:
  Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR gamma during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR gamma and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR gamma transcriptional activity leads to the induction of H4K20me1 modification of PPAR gamma and its targets and thereby promotes adipogenesis. We also show that PPAR gamma targets PPAR gamma2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.


systematic_name: M2417
exact_source: Table 1S_3
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters bound by both PPARG and RXRA [GeneID=5468, 6256] at 8 day time point of adipocyte differentiation of 3T3-L1 cells (preadipocyte).

description_full:
[cell repeats an earlier one in this file: 1327 characters]


systematic_name: M2420
exact_source: Table 3S
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with promoters bound by both PPARG and RXRA [GeneID=5468, 6256] at 8 (but not 0) day time point of adipocyte differentiation of 3T3-L1 cells (preadipocyte) and that were newly modified by H4K20me1.

description_full:
[cell repeats an earlier one in this file: 1327 characters]


systematic_name: M2432
exact_source: Table 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated during adipogenic differentiation of 3T3-L1 cells (preadipocyte) and down-regulated by troglitazone [PubChem=5591].

description_full:
  White adipose tissue (WAT) stores energy in the form of triglycerides, whereas brown tissue (BAT) expends energy, primarily by oxidizing lipids. WAT also secretes many cytokines and acute-phase proteins that contribute to insulin resistance in obese subjects. In this study, we have investigated the mechanisms by which activation of peroxisome proliferator-activated receptor gamma (PPARgamma) with synthetic agonists induces a brown phenotype in white adipocytes in vivo and in vitro. We demonstrate that this phenotypic conversion is characterized by repression of a set of white fat genes (visceral white), including the resistin, angiotensinogen, and chemerin genes, in addition to induction of brown-specific genes, such as Ucp-1. Importantly, the level of expression of the visceral white genes is high in mesenteric and gonadal WAT depots but low in the subcutaneous WAT depot and in BAT. Mutation of critical amino acids within helix 7 of the ligand-binding domain of PPARgamma prevents inhibition of visceral white gene expression by the synthetic agonists and therefore shows a direct role for PPARgamma in the repression process. Inhibition of the white adipocyte genes also depends on the expression of C/EBPalpha and the corepressors, carboxy-terminal binding proteins 1 and 2 (CtBP1/2). The data further show that repression of resistin and angiotensinogen expression involves recruitment of CtBP1/2, directed by C/EBPalpha, to the minimal promoter of the corresponding genes in response to the PPARgamma ligand. Developing strategies to enhance the brown phenotype in white adipocytes while reducing secretion of stress-related cytokines from visceral WAT is a means to combat obesity-associated disorders.


description_brief: Transcripts dependent upon IRS1 and IRS2 [GeneID=3667, 8660] for normal expression in liver.
systematic_name: M2434
exact_source: Fig. 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  We used a Cre-loxP approach to generate mice with varied expression of hepatic Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient homeostasis. While nutrient-sensitive transcripts were expressed nearly normally in liver lacking Irs2 (LKO2 mice), these transcripts were significantly dysregulated in liver lacking Irs1 (LKO1 mice) or Irs1 and Irs2 together (DKO mice). Similarly, a set of key gluconeogenic and lipogenic genes was regulated nearly normally by feeding in liver retaining a single Irs1 allele without Irs2 (DKO/1 mice) but was poorly regulated in liver retaining one Irs2 allele without Irs1 (DKO/2 mice). DKO/2 mice, but not DKO/1 mice, also showed impaired glucose tolerance and insulin sensitivity-though both Irs1 and Irs2 were required to suppress hepatic glucose production during hyperinsulinemic-euglycemic clamp. In contrast, either hepatic Irs1 or Irs2 mediated suppression of HGP by intracerebroventricular insulin infusion. After 12 weeks on a high-fat diet, postprandial tyrosine phosphorylation of Irs1 increased in livers of control and LKO2 mice, whereas tyrosine phosphorylation of Irs2 decreased in control and LKO1 mice. Moreover, LKO1 mice -- but not LKO2 mice -- that were fed a high-fat diet developed postprandial hyperglycemia. We conclude that Irs1 is the principal mediator of hepatic insulin action that maintains glucose homeostasis.


systematic_name: M2443
exact_source: Table 3S: 1h TGFB1 treated vs untreated: Fold change > 0
source_species_code: MM
GEO_id: GSE15871
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MEF cells (embryonic fibroblast) upon stimulation with TGFB1 [GeneID=7040] for 1 h.

description_full:
  Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.


systematic_name: M2445
exact_source: Table 3S: 10h TGFB1 treated vs untreated: Fold change > 0
source_species_code: MM
GEO_id: GSE15871
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in MEF cells (embryonic fibroblast) upon stimulation with TGFB1 [GeneID=7040] for 10 h.

description_full:
  Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.


systematic_name: M2458
exact_source: Fig. 1D: upper panel
source_species_code: MM
GEO_id: GSE17865
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Hepatic genes regulated by fasting or in response to WY14643 [PubChem=5694] and which require intact PPARA [GeneID=5465].

description_full:
  Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.


systematic_name: M2460
exact_source: Table 2
source_species_code: MM
GEO_id: GSE18172
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes downregulated in the postnatal day 3 pancreata with impaired function of GLIS3 [GeneID=169792].

description_full:
  Chromatin assembly factor 1 (CAF-1) deposits histones H3 and H4 rapidly behind replication forks through an interaction with the proliferating cell nuclear antigen (PCNA), a DNA polymerase processivity factor that also binds to a number of replication enzymes and other proteins that act on nascent DNA. The mechanisms that enable CAF-1 and other PCNA-binding proteins to function harmoniously at the replication fork are poorly understood. Here we report that the large subunit of human CAF-1 (p150) contains two distinct PCNA interaction peptides (PIPs). The N-terminal PIP binds strongly to PCNA in vitro but, surprisingly, is dispensable for nucleosome assembly and only makes a modest contribution to targeting p150 to DNA replication foci in vivo. In contrast, the internal PIP (PIP2) lacks one of the highly conserved residues of canonical PIPs and binds weakly to PCNA. Surprisingly, PIP2 is essential for nucleosome assembly during DNA replication in vitro and plays a major role in targeting p150 to sites of DNA replication. Unlike canonical PIPs, such as that of p21, the two p150 PIPs are capable of preferentially inhibiting nucleosome assembly, rather than DNA synthesis, suggesting that intrinsic features of these peptides are part of the mechanism that enables CAF-1 to function behind replication forks without interfering with other PCNA-mediated processes.


systematic_name: M2483
exact_source: Fig. 6C
source_species_code: MM
GEO_id: E-MEXP-2097
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes with known mitosis function that were down-regulated in MEF cells (embryonic fibroblast) upon knockout of LIN9 [GeneID=286826].

description_full:
  The retinoblastoma tumor suppressor protein (pRB) and related p107 and p130 pocket proteins function together with the E2F transcription factors to repress gene expression during the cell cycle and development. Recent biochemical studies have identified the multisubunit DREAM pocket protein complexes in Drosophila melanogaster and Caenorhabditis elegans in regulating developmental gene repression. Although a conserved DREAM complex has also been identified in mammalian cells, its physiological function in vivo has not been determined. Here we addressed this question by targeting Lin9, a conserved core subunit of DREAM. We found that LIN9 is essential for early embryonic development and for viability of adult mice. Loss of Lin9 abolishes proliferation and leads to multiple defects in mitosis and cytokinesis because of its requirement for the expression of a large set of mitotic genes, such as Plk1, Aurora A, and Kif20a. While Lin9 heterozygous mice are healthy and normal, they are more susceptible to lung tumorigenesis induced by oncogenic c-Raf than wild-type mice. Together these experiments provide the first direct genetic evidence for the role of LIN9 in development and mitotic gene regulation and they suggest that it may function as a haploinsufficient tumor suppressor.


systematic_name: M2511
exact_source: Table 1S: BMP7 / Control > 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in C3H10T1/2 cells (mesenchyme multipotent cells) upon their differentiation to brown adipocytes in response to BMP7 [GeneID=655].

description_full:
  Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and BMP signaling systems in brown adipogenesis, we examined the effect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a severe defect in differentiation. Treatment of these cells with BMP7 for 3 days prior to adipogenic induction restored differentiation and expression of brown adipogenic markers. The high level of adipogenic inhibitor preadipocyte factor 1 (Pref-1) in IRS-1-null cells was markedly reduced by 3 days of BMP7 treatment, and analysis of the 1.3-kb pref-1 promoter revealed 9 putative Smad binding elements (SBEs), suggesting that BMP7 could directly suppress Pref-1 expression, thereby allowing the initiation of the adipogenic program. Using a series of sequential deletion mutants of the pref-1 promoter linked to the luciferase gene and chromatin immunoprecipitation, we demonstrate that the promoter-proximal SBE (-192/-184) was critical in mediating BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance.


description_brief: Key proteins in mammalian autophagosome formation.
systematic_name: M2537
exact_source: Table 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Autophagy has been implicated in many physiological and pathological processes. Accordingly, there is a growing scientific need to accurately identify, quantify, and manipulate the process of autophagy. However, as autophagy involves dynamic and complicated processes, it is often analyzed incorrectly. In this Primer, we discuss methods to monitor autophagy and to modulate autophagic activity, with a primary focus on mammalian macroautophagy.


systematic_name: M3009
exact_source: Table 1
source_species_code: MM
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_brief:
  Genes up-regulated in liver from mice transgenic for SREBF1 or SREBF2 [GeneID = 6720, 6721] and down-regulated in mice lacking SCAP [GeneID=22937].

description_full:
  The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap-/- livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.


description_brief: Genes up-regulated in nasopharyngeal carcinoma (NPC) compared to the normal tissue.
systematic_name: M14427
exact_source: Table 1S
source_species_code: HS
GEO_id: GSE12452
contributor: Arthur Liberzon
contrib_organization: MSigDB Team
description_full:
  Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2B6, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region.


systematic_name: M4384
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M173 YWATTWNNRGCT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15719
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M52 YYCATTCAWW in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb].  The motif does not match any known transcription factor binding site.

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M11390
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M111 RACCACAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the RUNX1 [GeneSymbol=RUNX1] transcription factor binding site V$AML_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M13826
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M7 TGANTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the JUN [GeneSymbol=JUN] transcription factor binding site V$AP1_C (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M11668
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M15 CAGCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the REPIN1 [GeneSymbol=REPIN1] transcription factor binding site V$AP4_Q5 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9772
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M76 CAGGTA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF8 [GeneSymbol=TCF8] transcription factor binding site V$AREB6_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17997
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M14 TGACGTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF3 [GeneSymbol=ATF3] transcription factor binding site V$ATF3_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9955
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M9 TGAYRTCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ATF3 [GeneSymbol=ATF3] transcription factor binding site V$ATF3_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M11820
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M172 TTGCWCAAY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the CEBPB [GeneSymbol=CEBPB] transcription factor binding site V$CEBPB_02 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17214
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M23 TAATTA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the VSX1 [GeneSymbol=VSX1] transcription factor binding site V$CHX10_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6422
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M26 TTAYRTAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFIL3 [GeneSymbol=NFIL3] transcription factor binding site V$E4BP4_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3403
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M20 GTGACGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the E4F1 [GeneSymbol=E4F1] transcription factor binding site V$E4F1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17817
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M3 SCGGAAGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ELK1 [GeneSymbol=ELK1] transcription factor binding site V$ELK1_02 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M11396
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M25 TGACCTY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ESRRA [GeneSymbol=ESRRA] transcription factor binding site V$ERR1_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M14654
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M16 RYTTCCTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the ETS2 [GeneSymbol=ETS2] transcription factor binding site V$ETS2_B (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3746
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M36 RTAAACA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXF2 [GeneSymbol=FOXF2] transcription factor binding site V$FREAC2_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17925
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M11 MGGAAGTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GABPA [GeneSymbol=GABPA], GABPB2 [GeneSymbol=GABPB2] transcription factor binding site V$GABP_B (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7093
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M131 GATAAGR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$GATA_C (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M19368
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M94 TGATTTRY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the GFI1 [GeneSymbol=GFI1] transcription factor binding site V$GFI1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6517
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M139 AAAYWAACM in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXJ1 [GeneSymbol=FOXJ1] transcription factor binding site V$HFH4_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M12675
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M84 RGTTAMWNATT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TCF1 [GeneSymbol=TCF1] transcription factor binding site V$HNF1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M4764
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M83 TGTTTGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the FOXA1 [GeneSymbol=FOXA1] transcription factor binding site V$HNF3_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16482
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M141 TTCNRGNNNNTTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$HSF_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8746
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M68 RGAANNTTC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the HSF1 [GeneSymbol=HSF1] transcription factor binding site V$HSF1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M533
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M85 STTTCRNTTT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$IRF_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M482
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M73 CTTTGA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the LEF1 [GeneSymbol=LEF1] transcription factor binding site V$LEF1_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M829
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M61 YTAATTAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the LHX3 [GeneSymbol=LHX3] transcription factor binding site V$LHX3_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M822
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M33 YTATTTTNR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEF2A [GeneSymbol=MEF2A] transcription factor binding site V$MEF2_02 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3643
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M41 TGACAGNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEIS1 [GeneSymbol=MEIS1] transcription factor binding site V$MEIS1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9581
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M53 RYTGCNNRGNAAC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MIF [GeneSymbol=MIF] transcription factor binding site V$MIF1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8402
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M2 CACGTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYC [GeneSymbol=MYC] transcription factor binding site V$MYC_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M10806
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M35 GCANCTGNY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MYOD1 [GeneSymbol=MYOD1] transcription factor binding site V$MYOD_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M572
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M47 TGCCAAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NF1 [GeneSymbol=NF1] transcription factor binding site V$NF1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16911
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M55 TGGAAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFAT [GeneSymbol=NFAT], NFATC [GeneSymbol=NFATC] transcription factor binding site V$NFAT_Q4_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M8004
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M32 TGASTMAGC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFE2 [GeneSymbol=NFE2] transcription factor binding site V$NFE2_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1365
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M86 GGGNNTTTCC in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$NFKB_Q6_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9947
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M5 GATTGGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$NFY_Q6_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M9394
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M1 RCGCANGCGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NRF1 [GeneSymbol=NRF1] transcription factor binding site V$NRF1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M18169
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M44 YATGNWAAT in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the transcription factor binding site V$OCT_C (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15675
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M130 CCCNNGGGAR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the EBF2 [GeneSymbol=EBF2] transcription factor binding site V$OLF1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17318
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M70 CGTSACG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PAX3 [GeneSymbol=PAX3] transcription factor binding site V$PAX3_B (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1159
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M56 GGGTGGRR in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PAX4 [GeneSymbol=PAX4] transcription factor binding site V$PAX4_03 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M946
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M93 GGATTA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the PITX2 [GeneSymbol=PITX2] transcription factor binding site V$PITX2_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M15616
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M50 RGAGGAARY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SPI1 [GeneSymbol=SPI1] transcription factor binding site V$PU1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M16022
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M28 CTAWWWATA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEF2A [GeneSymbol=MEF2A] transcription factor binding site V$RSRFC4_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6568
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M54 TAAWWATAG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the MEF2A [GeneSymbol=MEF2A] transcription factor binding site V$RSRFC4_Q2 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M1630
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M38 TGACCTTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SF1 [GeneSymbol=SF1] transcription factor binding site V$SF1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7691
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M49 CATTGTYY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SOX9 [GeneSymbol=SOX9] transcription factor binding site V$SOX9_B1 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M18894
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M18 TCANNTGAY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SREBF1 [GeneSymbol=SREBF1] transcription factor binding site V$SREBP1_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M3827
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M121 CCAWWNAAGG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the SRF [GeneSymbol=SRF] transcription factor binding site V$SRF_Q4 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M6378
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M40 TTCYNRGAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the STAT5B [GeneSymbol=STAT5B] transcription factor binding site V$STAT5B_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M7521
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M51 TATAAA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TAF [GeneSymbol=TAF], TATA [GeneSymbol=TATA] transcription factor binding site V$TATA_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M613
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M67 TGANNYRGCA in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the NFE2L1 [GeneSymbol=NFE2L1], MAFG [GeneSymbol=MAFG] transcription factor binding site V$TCF11MAFG_01 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M17420
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M79 WGGAATGY in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the TEAD1 [GeneSymbol=TEAD1] transcription factor binding site V$TEF1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


systematic_name: M171
source_species_code: HS
contributor: Xiaohui Xie
contrib_organization: Broad Institute
description_brief:
  Genes having at least one occurrence of the highly conserved motif M10 GCCATNTTG in the regions spanning 4 kb centered on their transcription starting sites [-2kb, +2kb].  This matches the YY1 [GeneSymbol=YY1] transcription factor binding site V$YY1_Q6 (v7.4 TRANSFAC).

description_full:
[cell repeats an earlier one in this file: 987 characters]


description_brief: Genes upregulated in subsets of cells of a given type within various tumors
systematic_name: M46568
exact_source: 3CA Download meta_programs_2023-07-13: Malignant. 2 Cell Cycle - G1/S
external_details_URL: https://www.weizmann.ac.il/sites/3CA/
source_species_code: HS
contributor: Itay Tirosh
contrib_organization: Weizmann Institute of Science
description_full:
  In this study, an extensive analysis was conducted to define meta-programs (MPs) capturing intra-tumor heterogeneity across a spectrum of tumor types. The approach utilized non-negative matrix factorization (NMF) to analyze each cell type separately within individual tumor samples. This involved the analysis of malignant cells, macrophages, fibroblasts, endothelial cells, epithelial cells, T-cells, and B-cells. NMF was executed with varying parameter values (K=4, 5, 6, 7, 8, 9), thereby generating 39 programs for each cell type per sample. Each NMF program was summarized by the top 50 genes based on NMF coefficients.\nRobust MPs were then delineated for each cell type using a set of stringent criteria, including recurrence within the same tumor, similarity to programs in other tumors, and non-redundancy within a tumor. Subsequently, these robust NMF programs were clustered (per cell type) based on Jaccard similarity, leading to the identification of MPs associated with each cell type.\nTo enhance the quality of the MPs, a refinement steps were undertaken, involving the removal of MPs suspected of reflecting low-quality data (with an overrepresentation of ribosomal proteins or mitochondrial-encoded genes), single-study inclusion, or similarity to miss-annotated cell types.


description_brief: Neighborhood of ATRX
systematic_name: M10988
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)  in the MORF expression compendium


description_brief: Neighborhood of BNIP1
systematic_name: M2795
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BNIP1 BCL2/adenovirus E1B 19kDa interacting protein 1  in the MORF expression compendium


description_brief: Neighborhood of ERCC2
systematic_name: M404
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ERCC2 excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D)  in the MORF expression compendium


description_brief: Neighborhood of MDM2
systematic_name: M5734
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MDM2 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse)  in the MORF expression compendium


description_brief: Neighborhood of NF1
systematic_name: M6373
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease)  in the MORF expression compendium


description_brief: Neighborhood of PSMF1
systematic_name: M9093
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PSMF1 proteasome (prosome, macropain) inhibitor subunit 1 (PI31)  in the MORF expression compendium


description_brief: Neighborhood of RFC1
systematic_name: M17368
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of RFC1 replication factor C (activator 1) 1, 145kDa  in the MORF expression compendium


description_brief: Neighborhood of RFC5
systematic_name: M18618
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of RFC5 replication factor C (activator 1) 5, 36.5kDa  in the MORF expression compendium


description_brief: Neighborhood of STK17A
systematic_name: M5671
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of STK17A serine/threonine kinase 17a (apoptosis-inducing)  in the MORF expression compendium


description_brief: Neighborhood of TFDP2
systematic_name: M2022
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of TFDP2 transcription factor Dp-2 (E2F dimerization partner 2)  in the MORF expression compendium


description_brief: Neighborhood of MYC
systematic_name: M17328
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MYC v-myc myelocytomatosis viral oncogene homolog (avian)  in the MORF expression compendium


description_brief: Neighborhood of BMPR2
systematic_name: M14272
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase)  in the MORF expression compendium


description_brief: Neighborhood of CAMK4
systematic_name: M2749
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CAMK4 calcium/calmodulin-dependent protein kinase IV  in the MORF expression compendium


description_brief: Neighborhood of CASP10
systematic_name: M5177
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CASP10 caspase 10, apoptosis-related cysteine peptidase  in the MORF expression compendium


description_brief: Neighborhood of CASP2
systematic_name: M8508
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CASP2 caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2)  in the MORF expression compendium


description_brief: Neighborhood of CDC2L5
systematic_name: M18796
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CDC2L5 cell division cycle 2-like 5 (cholinesterase-related cell division controller)  in the MORF expression compendium


description_brief: Neighborhood of DDX11
systematic_name: M19243
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae)  in the MORF expression compendium


description_brief: Neighborhood of EIF4E
systematic_name: M18743
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of EIF4E eukaryotic translation initiation factor 4E  in the MORF expression compendium


description_brief: Neighborhood of ERCC4
systematic_name: M19749
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ERCC4 excision repair cross-complementing rodent repair deficiency, complementation group 4  in the MORF expression compendium


description_brief: Neighborhood of FLT1
systematic_name: M10328
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of FLT1 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)  in the MORF expression compendium


description_brief: Neighborhood of IKBKG
systematic_name: M15203
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of IKBKG inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma  in the MORF expression compendium


description_brief: Neighborhood of IL16
systematic_name: M19290
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of IL16 interleukin 16 (lymphocyte chemoattractant factor)  in the MORF expression compendium


description_brief: Neighborhood of ITGA2
systematic_name: M10073
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)  in the MORF expression compendium


description_brief: Neighborhood of JAK3
systematic_name: M7497
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of JAK3 Janus kinase 3 (a protein tyrosine kinase, leukocyte)  in the MORF expression compendium


description_brief: Neighborhood of KDR
systematic_name: M17652
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of KDR kinase insert domain receptor (a type III receptor tyrosine kinase)  in the MORF expression compendium


description_brief: Neighborhood of MAP3K14
systematic_name: M4205
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MAP3K14 mitogen-activated protein kinase kinase kinase 14  in the MORF expression compendium


description_brief: Neighborhood of MLLT10
systematic_name: M426
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MLLT10 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10  in the MORF expression compendium


description_brief: Neighborhood of MYL3
systematic_name: M1890
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow  in the MORF expression compendium


description_brief: Neighborhood of NOS2A
systematic_name: M8621
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of NOS2A nitric oxide synthase 2A (inducible, hepatocytes)  in the MORF expression compendium


description_brief: Neighborhood of ORC1L
systematic_name: M17184
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ORC1L origin recognition complex, subunit 1-like (yeast)  in the MORF expression compendium


description_brief: Neighborhood of PDPK1
systematic_name: M15051
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PDPK1 3-phosphoinositide dependent protein kinase-1  in the MORF expression compendium


description_brief: Neighborhood of PPP2R5B
systematic_name: M16012
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PPP2R5B protein phosphatase 2, regulatory subunit B (B56), beta isoform  in the MORF expression compendium


description_brief: Neighborhood of PRKACA
systematic_name: M16604
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PRKACA protein kinase, cAMP-dependent, catalytic, alpha  in the MORF expression compendium


description_brief: Neighborhood of PTEN
systematic_name: M17366
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1)  in the MORF expression compendium


description_brief: Neighborhood of PTPN9
systematic_name: M3297
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPN9 protein tyrosine phosphatase, non-receptor type 9  in the MORF expression compendium


description_brief: Neighborhood of PTPRB
systematic_name: M8747
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPRB protein tyrosine phosphatase, receptor type, B  in the MORF expression compendium


description_brief: Neighborhood of PTPRR
systematic_name: M17931
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPRR protein tyrosine phosphatase, receptor type, R  in the MORF expression compendium


description_brief: Neighborhood of REV3L
systematic_name: M887
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of REV3L REV3-like, catalytic subunit of DNA polymerase zeta (yeast)  in the MORF expression compendium


description_brief: Neighborhood of RUNX1
systematic_name: M5518
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)  in the MORF expression compendium


description_brief: Neighborhood of SS18
systematic_name: M18185
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SS18 synovial sarcoma translocation, chromosome 18  in the MORF expression compendium


description_brief: Neighborhood of SUPT3H
systematic_name: M7214
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SUPT3H suppressor of Ty 3 homolog (S. cerevisiae)  in the MORF expression compendium


description_brief: Neighborhood of THPO
systematic_name: M14178
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)  in the MORF expression compendium


description_brief: Neighborhood of THRA
systematic_name: M9866
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)  in the MORF expression compendium


description_brief: Neighborhood of TNFRSF25
systematic_name: M18296
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of TNFRSF25 tumor necrosis factor receptor superfamily, member 25  in the MORF expression compendium


description_brief: Neighborhood of TPR
systematic_name: M6400
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of TPR translocated promoter region (to activated MET oncogene)  in the MORF expression compendium


description_brief: Neighborhood of WNT1
systematic_name: M15256
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of WNT1 wingless-type MMTV integration site family, member 1  in the MORF expression compendium


description_brief: Neighborhood of ATM
systematic_name: M14967
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ATM ataxia telangiectasia mutated (includes complementation groups A, C and D)  in the GCM expression compendium


description_brief: Neighborhood of BNIP1
systematic_name: M19295
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BNIP1 BCL2/adenovirus E1B 19kDa interacting protein 1  in the GCM expression compendium


description_brief: Neighborhood of BECN1
systematic_name: M16495
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)  in the GCM expression compendium


description_brief: Neighborhood of SIRT2
systematic_name: M1706
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SIRT2 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae)  in the GCM expression compendium


description_brief: Neighborhood of BMPR2
systematic_name: M18257
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase)  in the GCM expression compendium


description_brief: Neighborhood of CASP2
systematic_name: M6471
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CASP2 caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2)  in the GCM expression compendium


description_brief: Neighborhood of CDH5
systematic_name: M15856
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CDH5 cadherin 5, type 2, VE-cadherin (vascular epithelium)  in the GCM expression compendium


description_brief: Neighborhood of CRKL
systematic_name: M7608
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CRKL v-crk sarcoma virus CT10 oncogene homolog (avian)-like  in the GCM expression compendium


description_brief: Neighborhood of DDX11
systematic_name: M13886
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae)  in the GCM expression compendium


description_brief: Neighborhood of DEAF1
systematic_name: M9098
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of DEAF1 deformed epidermal autoregulatory factor 1 (Drosophila)  in the GCM expression compendium


description_brief: Neighborhood of DFFA
systematic_name: M9388
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of DFFA DNA fragmentation factor, 45kDa, alpha polypeptide  in the GCM expression compendium


description_brief: Neighborhood of ERCC4
systematic_name: M4608
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ERCC4 excision repair cross-complementing rodent repair deficiency, complementation group 4  in the GCM expression compendium


description_brief: Neighborhood of FCGR2B
systematic_name: M13116
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of FCGR2B Fc fragment of IgG, low affinity IIb, receptor (CD32)  in the GCM expression compendium


description_brief: Neighborhood of IL6ST
systematic_name: M19045
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor)  in the GCM expression compendium


description_brief: Neighborhood of MAP4K4
systematic_name: M10191
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4  in the GCM expression compendium


description_brief: Neighborhood of MLL
systematic_name: M2457
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)  in the GCM expression compendium


description_brief: Neighborhood of MYCL1
systematic_name: M11890
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MYCL1 v-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived (avian)  in the GCM expression compendium


description_brief: Neighborhood of PPM1D
systematic_name: M11233
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PPM1D protein phosphatase 1D magnesium-dependent, delta isoform  in the GCM expression compendium


description_brief: Neighborhood of PRKAG1
systematic_name: M6594
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PRKAG1 protein kinase, AMP-activated, gamma 1 non-catalytic subunit  in the GCM expression compendium


description_brief: Neighborhood of PTPRD
systematic_name: M10475
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPRD protein tyrosine phosphatase, receptor type, D  in the GCM expression compendium


description_brief: Neighborhood of PTPRU
systematic_name: M931
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPRU protein tyrosine phosphatase, receptor type, U  in the GCM expression compendium


description_brief: Neighborhood of SMARCC1
systematic_name: M6968
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SMARCC1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 1  in the GCM expression compendium


description_brief: Neighborhood of SMARCD1
systematic_name: M3031
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SMARCD1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1  in the GCM expression compendium


description_brief: Neighborhood of SUPT4H1
systematic_name: M3473
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SUPT4H1 suppressor of Ty 4 homolog 1 (S. cerevisiae)  in the GCM expression compendium


description_brief: Neighborhood of UBE2N
systematic_name: M5805
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of UBE2N ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast)  in the GCM expression compendium


description_brief: Neighborhood of USP6
systematic_name: M191
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of USP6 ubiquitin specific peptidase 6 (Tre-2 oncogene)  in the GCM expression compendium


description_brief: Neighborhood of TNFRSF25
systematic_name: M10340
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of TNFRSF25 tumor necrosis factor receptor superfamily, member 25  in the CAR expression compendium


description_brief: Neighborhood of WBSCR22
systematic_name: M2326
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of WBSCR22 Williams Beuren syndrome chromosome region 22  in the CAR expression compendium


description_brief: Neighborhood of ATM
systematic_name: M8057
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ATM ataxia telangiectasia mutated (includes complementation groups A, C and D)  in the GNF2 expression compendium


description_brief: Neighborhood of BNIP2
systematic_name: M10599
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of BNIP2 BCL2/adenovirus E1B 19kDa interacting protein 2  in the GNF2 expression compendium


description_brief: Neighborhood of CASP4
systematic_name: M782
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CASP4 caspase 4, apoptosis-related cysteine peptidase  in the GNF2 expression compendium


description_brief: Neighborhood of CASP8
systematic_name: M1057
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CASP8 caspase 8, apoptosis-related cysteine peptidase  in the GNF2 expression compendium


description_brief: Neighborhood of CDKN1C
systematic_name: M14550
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)  in the GNF2 expression compendium


description_brief: Neighborhood of EGFR
systematic_name: M4193
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)  in the GNF2 expression compendium


description_brief: Neighborhood of HLA-C
systematic_name: M5267
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of HLA-C major histocompatibility complex, class I, C  in the GNF2 expression compendium


description_brief: Neighborhood of IGFBP1
systematic_name: M9592
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of IGFBP1 insulin-like growth factor binding protein 1  in the GNF2 expression compendium


description_brief: Neighborhood of INPP5D
systematic_name: M9268
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of INPP5D inositol polyphosphate-5-phosphatase, 145kDa  in the GNF2 expression compendium


description_brief: Neighborhood of ITGAL
systematic_name: M5802
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ITGAL integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)  in the GNF2 expression compendium


description_brief: Neighborhood of LYN
systematic_name: M11485
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog  in the GNF2 expression compendium


description_brief: Neighborhood of MYD88
systematic_name: M13614
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of MYD88 myeloid differentiation primary response gene (88)  in the GNF2 expression compendium


description_brief: Neighborhood of PTPN4
systematic_name: M16951
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPN4 protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte)  in the GNF2 expression compendium


description_brief: Neighborhood of PTPN6
systematic_name: M7957
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPN6 protein tyrosine phosphatase, non-receptor type 6  in the GNF2 expression compendium


description_brief: Neighborhood of PTPRC
systematic_name: M15369
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of PTPRC protein tyrosine phosphatase, receptor type, C  in the GNF2 expression compendium


description_brief: Neighborhood of SERPINB5
systematic_name: M9365
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SERPINB5 serpin peptidase inhibitor, clade B (ovalbumin), member 5  in the GNF2 expression compendium


description_brief: Neighborhood of SERPINI2
systematic_name: M5062
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of SERPINI2 serpin peptidase inhibitor, clade I (pancpin), member 2  in the GNF2 expression compendium


description_brief: Neighborhood of STAT6
systematic_name: M8633
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of STAT6 signal transducer and activator of transcription 6, interleukin-4 induced  in the GNF2 expression compendium


description_brief: Neighborhood of ZAP70
systematic_name: M1169
source_species_code: HS
contributor: Aravind Subramanian
contrib_organization: MSigDB Team
description_full:
  Neighborhood of ZAP70 zeta-chain (TCR) associated protein kinase 70kDa  in the GNF2 expression compendium


description_brief: Genes down-regulated in RK3E cells (kidney epithelium) over-expressing GLI1 [Gene ID=2735].
systematic_name: M2622
exact_source: Gli1 vs control; bottom 30 genes (diff. of means)
source_species_code: RN
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras-expressing cells established a set of genes unique to GLI1-induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras-expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus DNA-binding sequences were identified in the 5' regions of cyclin D2, IGFBP-6, osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were demonstrated in GLI1-amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1-induced cell transformation occurs through multiple downstream pathways.


description_brief: Genes down-regulated in BJAB (lymphoma) cells by rapamycin (sirolimus) [PubChem = 6610346].
systematic_name: M2643
exact_source: Rapa60 and Rapa120 vs ET60 and ET120; top 200 genes (diff. of means)
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.


systematic_name: M2646
exact_source: Table 1: Adhesion/Matrix/Cytoskeleton
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Matrix, adhesion or cytoskeleton genes induced by NF-kappaB in primary keratinocytes and fibroblasts.

description_full:
[cell repeats an earlier one in this file: 1186 characters]


systematic_name: M2648
exact_source: cyclin D1 (K112E) vs control; top 200 genes (diff-means)
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in MCF-7 cells (breast cancer) over-expressing a mutant K112E form of CCND1 [Gene ID=595] gene.

description_full:
[cell repeats an earlier one in this file: 717 characters]


description_full: 293 cells, infected with RCAS-beta-cateninS37A or RCAS-GFP
systematic_name: M2677
exact_source: beta-catenin S37A vs GFP; bottom 50 genes (mutual information)
source_species_code: HS
GEO_id: GSE1473
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HEK293 cells (kidney fibroblasts) expressing constitutively active form of CTNNB1 [Gene ID=1499] gene.


description_full: 293 cells, infected with RCAS-beta-cateninS37A or RCAS-GFP
systematic_name: M2678
exact_source: beta-catenin S37A vs GFP; top 50 genes (mutual information)
source_species_code: HS
GEO_id: GSE1473
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in HEK293 cells (kidney fibroblasts) expressing constitutively active form of CTNNB1 [Gene ID=1499] gene.


systematic_name: M2682
exact_source: ATF2-small vs Control; top 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE1059
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in myometrial cells over-expressing a shortened splice form of ATF2 [Gene ID=1386] gene.

description_full:
  Human myometrial cells taken from biopsies of pre-menopausal non-cancerous non-pregnant uteri were cultured in complete MEM D-valine medium plus 10% FCS, and stably-transfected with the pcDNA3.1/V5-His TOPO vector (Invitrogen) harbouring ATF2-small gene or a control empty-vector.


systematic_name: M2690
exact_source: Wnt-1 vs Controls; top 200 genes (diff. of means)
source_species_code: MM
GEO_id: GSE1899
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in C57MG cells (mammary epithelium) by over-expression of WNT1 [Gene ID=7471] gene.

description_full:
  Targets of Wnt-1 in C57MG. RNA from murine mammary C57MG cells transfected with an empty control vector (PLNCx) or an expression vector encoding Wnt-1 was isolated and analyzed on Affymetrix MG-U74Av2 arrays.


systematic_name: M2691
exact_source: ATM_siRNA_0 vs controls; bottom 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE1676
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HEK293 cells (kidney fibroblasts) upon knockdown of ATM [Gene ID=472] gene by RNAi.

description_full:
  Expression profiling of cells knocked-down for ATM and control un-infected cells and cells infected with siRNA against LacZ.


systematic_name: M2692
exact_source: ATM_siRNA_0 vs controls; top 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE1676
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in HEK293 cells (kidney fibroblasts) upon knockdown of ATM [Gene ID=472] gene by RNAi.

description_full:
  Expression profiling of cells knocked-down for ATM and control un-infected cells and cells infected with siRNA against LacZ.


systematic_name: M2693
exact_source: p53_siRNA vs controls; bottom 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE1676
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HEK293 cells (kidney fibroblasts) upon knockdown of TP53 [Gene ID=7157] gene by RNAi.

description_full:
  Expression profiling of cells knocked-down for p53 and control un-infected cells and cells infected with siRNA against LacZ.


systematic_name: M2695
exact_source: RELA shRNA vs WT; bottom 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE1676
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HEK293 cells (kidney fibroblasts) upon knockdown of RELA [Gene ID=5970] gene by RNAi.

description_full:
  Expression profiling of cells knocked-down for RelA and control un-infected cells and cells infected with siRNA against LacZ.


systematic_name: M2702
exact_source: activated CTNNB1 vs GFP; bottom 50 genes (mutual information)
source_species_code: HS
GEO_id: GSE3151
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in primary epithelial breast cancer cell culture over-expressing activated CTNNB1 [Gene ID=1499] gene.

description_full:
[cell repeats an earlier one in this file: 155 characters]


systematic_name: M2703
exact_source: activated CTNNB1 vs GFP; top 50 genes (mutual information)
source_species_code: HS
GEO_id: GSE3151
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in primary epithelial breast cancer cell culture over-expressing activated CTNNB1 [Gene ID=1499] gene.

description_full:
[cell repeats an earlier one in this file: 155 characters]


systematic_name: M2706
exact_source: E2F3 vs GFP; top 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE3151
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in primary epithelial breast cancer cell culture over-expressing E2F3 [Gene ID=1871] gene.

description_full:
[cell repeats an earlier one in this file: 155 characters]


systematic_name: M2719
exact_source: cAMP vs WT; bottom 150 genes (diff. of means)
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in primary thyrocyte cultures in response to cAMP signaling pathway activation by thyrotropin (TSH).


systematic_name: M2720
exact_source: cAMP vs WT; top 150 genes (diff. of means)
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in primary thyrocyte cultures in response to cAMP signaling pathway activation by thyrotropin (TSH).


description_brief: Genes down-regulated in JNK inhibitor-treated (SP600125[PubChem=8515]) keratinocytes.
systematic_name: M2745
exact_source: SP600125 experiment CONTROL vs TREATED; top 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE4828
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  Keratinocytes are grown to ~75% confluence and either treated with 5nM SP600125, or left untreated. Samples are harvested 1, 4, 24 and 48 h post-treatment.


description_full: MCF10A cells in 3-D culture for 15 h after treatment with BRCA1-RNAi vs Luc-RNAi adenovirus
systematic_name: M2748
exact_source: BRCA1 KD vs LUC KD; top 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE4750
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in MCF10A cells (breast cancer) upon knockdown of BRCA1 [Gene ID=672] gene by RNAi.


description_full: MCF10A cells in 3-D culture for 15 h after treatment with CtIP-RNAi vs Luc-RNAi adenovirus.
systematic_name: M2752
exact_source: CTIP 20 vs LUC 20 KD; top 150 genes (diff. of means)
source_species_code: HS
GEO_id: GSE4751
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in MCF10A cells (breast cancer) upon knockdown of RBBP8 [Gene ID=RBBP8] gene by RNAi.


systematic_name: M2756
exact_source: contol (DMSO) vs 24h of rapamycin treatment; bottom 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE5821
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in CEM-C1 cells (T-CLL) in comparison of control vs rapamycin (sirolimus) [PubChem=6610346], an mTOR pathway inhibitor.

description_full:
  CEM-C1 cells were treated with 10 nM rapamycin or DMSO and harvested for microarray analysis at 24 hours


systematic_name: M2762
exact_source: DCA vs Controls; top 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE6014
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in A549 lung carcinoma and M059K glioblastoma cells treated with dichloroacetate [PubChem=6597].

description_full:
  Analysis of A549 lung carcinoma and M059K glioblastoma cells treated with dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase. DCA shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential in cancer cells.


systematic_name: M2764
exact_source: Early (12, 18 and 24 h) vs control; top 200 genes (diff. of means)
source_species_code: MM
GEO_id: GSE3749
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated during early stages of differentiation of embryoid bodies from J1 embryonic stem cells.

description_full:
  An 11-point time course study on differentiating embryoid bodies from a murine J1 embryonic stem cell line. The time course includes 0 hr, 6 hr, 12 hr, 18 hr, 24 hr, 36 hr, 48 hr, 4 days, 7 days, 9 days and 14 days.


systematic_name: M2768
exact_source: Late (4, 7 and 9 days) vs control; top 200 genes (diff. of means)
source_species_code: MM
GEO_id: GSE3749
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated during late stages of differentiation of embryoid bodies from J1 embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 215 characters]


systematic_name: M2770
exact_source: Early (12, 18 and 24 h) vs control; top 200 genes (diff. of means)
source_species_code: MM
GEO_id: GSE3231
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated during early stages of differentiation of embryoid bodies from V6.5 embryonic stem cells.

description_full:
  An 11-point time course study comparing V6.5 embryonic stem cells versus embryoid bodies. Time course 0 hours, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 4 days, 7 days, 9 days, and 14 days.


systematic_name: M2772
exact_source: Late (4, 7 and 9 days) vs control; top 200 genes (diff. of means)
source_species_code: MM
GEO_id: GSE3231
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated during late stages of differentiation of embryoid bodies from V6.5 embryonic stem cells.

description_full:
[cell repeats an earlier one in this file: 206 characters]


systematic_name: M2788
exact_source: Control vs DAPT; top 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE6495
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in MOLT4 cells (T-ALL) by DAPT [PubChem=16219261], an inhibitor of NOTCH signaling pathway.

description_full:
  NOTCH signaling in T-ALL cell lines. Three independent cultures of the MOLT4 cell line before and 48 hours after addition of the gamma-secretase inhibitor DAPT (5 uM).


systematic_name: M2790
exact_source: overexpression of eIFGI vs control; top 100 genes (diff. of means)
source_species_code: HS
GEO_id: GSE6043
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HMEC cells (primary mammary epithelium) upon over-expression of EIF4E [Gene ID=1977] gene.

description_full:
  Translation initiation factor 4E confers primary human cells with neoplastic properties. A comparison of HMEC/hTERT and HMEC/hTERT/eIF4E cells using both total and polyribosoaml associated RNA.


systematic_name: M2791
exact_source: overexpression of eIFGI vs control; top 100 genes (diff. of means)
source_species_code: HS
GEO_id: GSE6043
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in HMEC cells (primary mammary epithelium) upon over-expression of EIF4E [Gene ID=1977] gene.

description_full:
  Translation initiation factor 4E confers primary human cells with neoplastic properties. A comparison of HMEC/hTERT and HMEC/hTERT/eIF4E cells using both total and polyribosoaml associated RNA.


description_brief: Genes down-regulated in retina cells from CRX [Gene ID=1406] knockout mice.
systematic_name: M2792
exact_source: Crx-/- mouse retina cells vs Controls; bottom 150 genes (diff. of means)
source_species_code: MM
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  Complete microarray datasets for wild-type vs. Crx-/- comparison at P21 are in Supplementary Table S5. This table contains the full microarray datasets from six microarray hybridizations (three biological replicates each from wild-type (129S6/SvEv) and Crx-/- retinas at P21). The data from each of the individual microarray experiments are labeled with the following prefixes:Crx-mut_#1i etc. and129-wt-P21-#1i etc.


description_brief: Genes down-regulated in retina cells from CRX and NRL [Gene ID=1406, 4901] double knockout mice.
systematic_name: M2794
exact_source: Crx -/- & Nrl-/- mouse retina cells vs Controls; top 150 genes (diff. of means)
source_species_code: MM
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  Complete microarray datasets for wild-type vs. Crx-/-; Nrl-/- comparison at P21 are in Supplementary Table S6. This table contains the full microarray datasets from nine microarray hybridizations (three biological replicates each from wild-type (C57BL/6), wild-type (129S6/SvEv) and Crx-/-; Nrl-/- retinas at P21). Since Crx-/-; Nrl-/- is on a mixed 129 X B6 background, we present comparisons between both of the individual wild-type mutant backgrounds (as data from the mixed control background were not available). The data from each of the individual microarray experiments are labeled with the following prefixes:Crx-mut_#1i etc.,B6-wt-P21-#1i etc. and129-wt-P21-#1i etc.


description_brief: Genes down-regulated in retina cells from NRL [Gene ID=4901] knockout mice.
systematic_name: M2797
exact_source: Nrl-/- mouse retina cells vs Controls; bottom 150 genes (diff. of means)
source_species_code: MM
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation.


systematic_name: M2801
exact_source: RB -/- & p107-/-; bottom 150 genes (diff. of means)
source_species_code: MM
GEO_id: GSE9562
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in primary keratinocytes from RB1 and RBL1 [Gene ID=5925, 5933] skin specific knockout mice.

description_full:
[cell repeats an earlier one in this file: 1130 characters]


systematic_name: M2803
exact_source: RB -/- & p130-/-; bottom 150 genes (diff. of means)
source_species_code: MM
GEO_id: GSE9562
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in primary keratinocytes from RB1 and RBL2 [Gene ID=5925, 5934] skin specific knockout mice.

description_full:
[cell repeats an earlier one in this file: 1130 characters]


systematic_name: M2818
source_species_code: HS
GEO_id: GSE8685
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in Sez-4 cells (T lymphocyte) that were first starved of IL2 [Gene ID=3558] and then stimulated with IL15 [Gene ID=3600].

description_full:
  Sez-4 cell line was starved of IL2 for 16h, washed twice and placed into 6-well plates in 10ml RPMI (10% FBS) for 2 h followed by addition of IL-15 (20ng/mL) or medium alone for 4 h.

exact_source:
  Sez-4 cells starved of IL-2 and activated with IL-15 vs Sez-4 cells starved of IL-2; bottom 200 genes (diff. of means)


systematic_name: M2820
source_species_code: HS
GEO_id: GSE8685
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in Sez-4 cells (T lymphocyte) that were first starved of IL2 [Gene ID=3558] and then stimulated with IL2 [Gene ID=3558].

description_full:
  Sez-4 cell line was starved of IL2 for 16h, washed twice and placed into 6-well plates in 10ml RPMI (10% FBS) for 2 h followed by addition of IL-2 (200U) or medium alone for 4 h.

exact_source:
  Sez-4 cells starved of IL-2 and activated with IL-2 vs Sez-4 cells starved of IL-2; bottom 200 genes (diff. of means)


systematic_name: M2824
source_species_code: HS
GEO_id: GSE8685
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in Sez-4 cells (T lymphocyte) that were first starved of IL2 [Gene ID=3558] and then stimulated with IL21 [Gene ID=59067].

description_full:
  Sez-4 cell line was starved of IL2 for 16h, washed twice and placed into 6-well plates in 10ml RPMI (10% FBS) for 2 h followed by addition of IL-21 (100 ng/ml) or medium alone for 4 h.

exact_source:
  Sez-4 cells starved of IL-2 and activated with IL-21 vs Sez-4 cells starved of IL-2; bottom 200 genes (diff. of means)


systematic_name: M2828
exact_source: PDGF stimulation after ERL inhibition vs Controls; bottom 300 genes (diff. of means)
source_species_code: HS
GEO_id: GSE7403
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in SH-SY5Y cells (neuroblastoma) in response to PDGF [Gene ID=] stimulation after pre-treatment with the ERK inhibitors U0126 and PD98059 [PubChem=3006531, 4713].

description_full:
  To define ERK/PDGFR activation signature, SH-SY5Y cells were grown to confluence and starved overnight in serum-free medium in order to silence any sustained effects from growth factor signaling. Prior to induction with 50ng/ml PDGF, cells were treated with pathway inhibitors 74 mM Apigenin or 50 mM U0126, or with DMSO (carrier) for 60 minutes. Total RNA was isolated 30 minutes after PDGF addition. Experiments were performed in duplicate. The RNA was processed and hybridized with Affymetrix U133A GeneChips.


systematic_name: M2830
exact_source: PDGF stimulation after ERL inhibition vs Controls; top 300 genes (diff. of means)
source_species_code: HS
GEO_id: GSE7403
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in SH-SY5Y cells (neuroblastoma) in response to PDGF [Gene ID=] stimulation after pre-treatment with the ERK inhibitors U0126 and PD98059 [PubChem=3006531, 4713].

description_full:
  To define ERK/PDGFR activation signature, SH-SY5Y cells were grown to confluence and starved overnight in serum-free medium in order to silence any sustained effects from growth factor signaling. Prior to induction with 50ng/ml PDGF, cells were treated with pathway inhibitors 74 mM Apigenin or 50 mM U0126, or with DMSO (carrier) for 60 minutes. Total RNA was isolated 30 minutes after PDGF addition. Experiments were performed in duplicate. The RNA was processed and hybridized with Affymetrix U133A GeneChips.


description_brief: Genes down-regulated in MCF10A cells (breast cancer) over-expressing YAP1 [Gene ID=10413] gene.
systematic_name: M2841
exact_source: YAP1 vs control; bottom 50 genes
source_species_code: HS
GEO_id: GSE10196
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  MCF10A cells were infected with retrovirus constructs (vector or YAP) and puromycin was used to select for transduced cells. Cells were split and grown to ~60-75%% confluency at which point they were harvested for RNA. Vector vs. YAP comparison was done in duplicate.


description_brief: Genes down-regulated in MCF10A cells vs knockdown of EIF4G1 [Gene ID=1981] gene by RNAi.
systematic_name: M2846
exact_source: control vs RNAi KD eIFGI; bottom 100 genes (diff. of means)
source_species_code: HS
GEO_id: GSE11011
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  eIF4GI Links Nutrient Sensing by mTOR to Cell Proliferation and Inhibition of Autophagy. Two sets of experiments are presented. First, overall transcriptome changes were determined for control or eIF4GI silenced cells. Next, mRNAs associated with polysomes were compared between control and eIF4GI silenced cells.


description_brief: Genes defining the KRAS [Gene ID=3845] dependency signature.
systematic_name: M2851
exact_source: Fig. 5B
source_species_code: HS
GEO_id: GSE15126
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  K-ras mutations occur frequently in epithelial cancers. Using short hairpin RNAs to deplete K-Ras in lung and pancreatic cancer cell lines harboring K-ras mutations, two classes were identified-lines that do or do not require K-Ras to maintain viability. Comparing these two classes of cancer cells revealed a gene expression signature in K-Ras-dependent cells, associated with a well-differentiated epithelial phenotype, which was also seen in primary tumors. Several of these genes encode pharmacologically tractable proteins, such as Syk and Ron kinases and integrin beta6, depletion of which induces epithelial-mesenchymal transformation (EMT) and apoptosis specifically in K-Ras-dependent cells. These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in K-Ras-addicted cancers represent candidate therapeutic targets.


systematic_name: M2853
exact_source: control vs KD STK33 in nomo & skm cells; bottom 300 genes (diff. of means)
source_species_code: HS
GEO_id: GSE15151
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in NOMO-1 and SKM-1 cells (AML) after knockdown of STK33 [Gene ID=65975] by RNAi.

description_full:
  NOMO-1 and SKM-1 acute myeloid leukemia (AML) cells were stably transduced with different pLKO.1puro lentiviral shRNA vectors targeting STK33 or a nontargeting control shRNA. VSV-G-pseudotyped lentiviral particles were produced by cotransfection of 293T cells with pLKO.1 constructs and the compatible packaging plasmids pMD.G and pCMVR8.91. Virus was harvested 48 and 72 hours after transfection, cells were incubated with lentiviral supernatants for 30 hours, and infected cells were selected with 2ug/ml puromycin. RNA was isolated after 2 days of puromycin selection and isolation of viable cells by density gradient centrifugation, and gene expression was profiled using GeneChip Human Genome U133 Plus 2.0 microarrays (Affymetrix).


systematic_name: M2870
exact_source: Knockout of NERF2 vs control; down-regulated genes
source_species_code: MM
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in MEF cells (embryonic fibroblasts) after knockout of NFE2L2 [Gene ID=4780] gene.

description_full:
  The transcription factor NRF2 (NFE2L2), induces a cytoprotective response to oxidative stresses and its mutations confer constitutive activation in cancer. We generated a gene set representing activation of NFE2L2, as represented by genes downregulated by NFE2L2 knockout using the data from Malhotra et al. D, et al. Nucleic Acids Res. 2010;38:5718-5734.


description_brief: YAP conserved signature.
systematic_name: M2871
exact_source: Table S3
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  Cancer stem cells (CSCs) are proposed to drive tumor initiation and progression. Yet, our understanding of the cellular and molecular mechanisms that underlie CSC properties is limited. Here we show that the activity of TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in breast CSCs. TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value. Gain of TAZ endows self-renewal capacity to non-CSCs. In epithelial cells, TAZ forms a complex with the cell-polarity determinant Scribble, and loss of Scribble--or induction of the epithelial-mesenchymal transition (EMT)--disrupts the inhibitory association of TAZ with the core Hippo kinases MST and LATS. This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity


systematic_name: M2872
exact_source: JAK2_sh vs controls; bottom 200 genes
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes down-regulated in HEL cells (erythroleukemia) after knockdown of JAK2 [Gene ID=3717] gene by RNAi.


systematic_name: M2873
exact_source: JAK2_sh vs controls; top 200 genes
source_species_code: HS
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_brief:
  Genes up-regulated in HEL cells (erythroleukemia) after knockdown of JAK2 [Gene ID=3717] gene by RNAi.


description_brief: Genes down-regulated in HUVEC cells (endothelium) by treatment with PGF [Gene ID=5228].
systematic_name: M2673
exact_source: PGF vs control; bottom 200 genes (diff. of means)
source_species_code: HS
GEO_id: GSE837
contributor: Pablo Tamayo
contrib_organization: Broad Institute
description_full:
  HUVECs (human umbilical cord vein endothelial cells) are treated with the angiogenic factor PlGF (alias of PGF, placental growth factor) in low or high serum media.


systematic_name: M3012
exact_source: GSE1000001_1574_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in naïve CD8 T cells compared to effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection).

description_full:
  How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after viral clearance in accordance with changes in CD8 T cell functional properties. Even though memory cell precursors were present at the peak of the immune response, these cells did not display hallmark functional traits of memory T cells. However, these cells gradually acquired the memory cell qualities of self-renewal and rapid recall to antigen suggesting the model that antigen-specific CD8 T cells progressively differentiate into memory cells following viral infection.


systematic_name: M3013
exact_source: GSE1000001_1574_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in naïve CD8 T cells compared to effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection).

description_full:
  How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after viral clearance in accordance with changes in CD8 T cell functional properties. Even though memory cell precursors were present at the peak of the immune response, these cells did not display hallmark functional traits of memory T cells. However, these cells gradually acquired the memory cell qualities of self-renewal and rapid recall to antigen suggesting the model that antigen-specific CD8 T cells progressively differentiate into memory cells following viral infection.


systematic_name: M3014
exact_source: GSE1000001_1575_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in naïve CD8 T cells compared to effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection).

description_full:
  How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after viral clearance in accordance with changes in CD8 T cell functional properties. Even though memory cell precursors were present at the peak of the immune response, these cells did not display hallmark functional traits of memory T cells. However, these cells gradually acquired the memory cell qualities of self-renewal and rapid recall to antigen suggesting the model that antigen-specific CD8 T cells progressively differentiate into memory cells following viral infection.


systematic_name: M3017
exact_source: GSE1000001_1575_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in naïve CD8 T cells compared to effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3020
exact_source: GSE1000001_1576_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in naïve CD8 T cells compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3022
exact_source: GSE1000001_1576_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in naïve CD8 T cells compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3023
exact_source: GSE1000001_1577_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection) compared to effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3025
exact_source: GSE1000001_1577_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection) compared to effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3027
exact_source: GSE1000001_1578_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection) compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3028
exact_source: GSE1000001_1578_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in effector CD8 T cells at the peak expansion phase (day 8 after LCMV-Armstrong infection) compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3030
exact_source: GSE1000001_1579_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection) compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


systematic_name: M3032
exact_source: GSE1000001_1579_200_DN
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in effector CD8 T cells at contraction phase (day 15 after LCMV-Armstrong infection) compared to memory CD8 T cells (day 40+ after LCMV-Armstrong infection).

description_full:
[cell repeats an earlier one in this file: 792 characters]


description_brief: Genes up-regulated in comparison of naïve CD8 T cells versus effector CD8 T cells.
systematic_name: M3035
exact_source: GSE1000002_1580_200_UP
source_species_code: MM
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8(+) T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8(+) T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8(+) T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level.


systematic_name: M3046
exact_source: GSE10094_1068_200_UP
source_species_code: MM
GEO_id: GSE10094
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of CD4 [GeneID=920] T cells from mice challenged with LCMV versus those challenged with Listeria-gp61.

description_full:
  Following infection with LCMV, CD4+ SMARTA TCR transgenic cells (specific for the gp61-80 epitope of the LCMV glycoprotein) rapidly expand, become effector cells, and go on to form a long-lived memory population. Following infection with a recombinant Listeria monocytogenes expressing the LCMV epitope gp61-80, SMARTA cells also expand but display defective effector differentiation and fail to form memory. In an attempt to understand the signals required for CD4 T cell memory differentiation, we compared gene expression by SMARTA cells at the peak of the primary response following either Lm-gp61 or LCMV infection.


systematic_name: M3047
exact_source: GSE10094_1068_200_DN
source_species_code: MM
GEO_id: GSE10094
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] T cells from mice challenged with LCMV versus those challenged with Listeria-gp61.

description_full:
  Following infection with LCMV, CD4+ SMARTA TCR transgenic cells (specific for the gp61-80 epitope of the LCMV glycoprotein) rapidly expand, become effector cells, and go on to form a long-lived memory population. Following infection with a recombinant Listeria monocytogenes expressing the LCMV epitope gp61-80, SMARTA cells also expand but display defective effector differentiation and fail to form memory. In an attempt to understand the signals required for CD4 T cell memory differentiation, we compared gene expression by SMARTA cells at the peak of the primary response following either Lm-gp61 or LCMV infection.


description_brief: Genes up-regulated in comparison of naive CD8 T cells versus memory CD8 T cells.
systematic_name: M3048
exact_source: GSE10239_1247_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation


systematic_name: M3050
exact_source: GSE10239_1248_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of naive CD8 T cells versus effector CD8 T cells KLRG1 Int [GeneID=10219].

description_full:
  Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation


systematic_name: M3051
exact_source: GSE10239_1248_200_DN
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of naive CD8 T cells versus effector CD8 T cells KLRG1 Int [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3052
exact_source: GSE10239_1249_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of naive CD8 T cells versus effector CD8 T cells KLRG1 high [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3054
exact_source: GSE10239_1249_200_DN
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of naive CD8 T cells versus effector CD8 T cells KLRG1 high [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3055
exact_source: GSE10239_1250_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of memory CD8 T cells versus effector CD8 T cells KLRG1 intermediate [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3059
exact_source: GSE10239_1250_200_DN
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of memory CD8 T cells versus effector CD8 T cells KLRG1 intermediate [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3060
exact_source: GSE10239_1251_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of memory CD8 T cells versus effector CD8 T cells KLRG1 high [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3067
exact_source: GSE10239_1251_200_DN
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of memory CD8 T cells versus effector CD8 T cells KLRG1 high [GeneID=10219].

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3068
exact_source: GSE10239_1252_200_UP
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of effector CD8 T cells KRLG1 Int [GeneID=10219] vs those with KRLG1 Hi.

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3070
exact_source: GSE10239_1252_200_DN
source_species_code: MM
GEO_id: GSE10239
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of effector CD8 T cells KRLG1 Int [GeneID=10219] vs those with KRLG1 Hi.

description_full:
[cell repeats an earlier one in this file: 1092 characters]


systematic_name: M3076
exact_source: GSE10325_1069_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of healthy CD4 [GeneID=920] T cells versus healthy CD19 [GeneID=920] B cells.

description_full:
  Gene expression profile studies have identified an interferon signature in whole blood or mononuclear cell samples from patients with systemic lupus erythematosus. This study was designed to determine whether specific lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus patients demonstrated unique gene expression profiles compared to subsets isolated from healthy controls.


systematic_name: M3077
exact_source: GSE10325_1069_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of healthy CD4 [GeneID=920] T cells versus healthy CD19 [GeneID=920] B cells.

description_full:
  Gene expression profile studies have identified an interferon signature in whole blood or mononuclear cell samples from patients with systemic lupus erythematosus. This study was designed to determine whether specific lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus patients demonstrated unique gene expression profiles compared to subsets isolated from healthy controls.


systematic_name: M3079
exact_source: GSE10325_1070_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of healthy CD4 [GeneID=920] T cells versus healthy myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3084
exact_source: GSE10325_1072_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of systemic lupus erythematosus CD4 [GeneID=920] T cells versus systemic lupus erythematosus B cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3085
exact_source: GSE10325_1072_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of systemic lupus erythematosus CD4 [GeneID=920] T cells versus systemic lupus erythematosus B cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3087
exact_source: GSE10325_1073_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of systemic lupus erythematosus CD4 [GeneID=920] T cells versus systemic lupus erythematosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3088
exact_source: GSE10325_1073_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of systemic lupus erythematosus CD4 [GeneID=920] T cells versus systemic lupus erythematosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3089
exact_source: GSE10325_1074_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of systemic lupus erythematosus B cells versus systemic lupus erythromatosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3091
exact_source: GSE10325_1074_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of systemic lupus erythematosus B cells versus systemic lupus erythromatosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3092
exact_source: GSE10325_1075_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of healthy CD4 [GeneID=920] T cells versus systemic lupus erythematosus CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3093
exact_source: GSE10325_1075_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of healthy CD4 [GeneID=920] T cells versus systemic lupus erythematosus CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3096
exact_source: GSE10325_1077_200_UP
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of healthy myeloid cells versus systemic lupus erythematosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3097
exact_source: GSE10325_1077_200_DN
source_species_code: HS
GEO_id: GSE10325
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of healthy myeloid cells versus systemic lupus erythematosus myeloid cells.

description_full:
[cell repeats an earlier one in this file: 418 characters]


systematic_name: M3098
exact_source: GSE10463_1742_200_UP
source_species_code: HS
GEO_id: GSE10463
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of dendritic cells activated in the absense of VAF347 [PubChem=10172275] versus those activated in the presence of VAF347 [PubChem=10172275].

description_full:
  VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compound’s ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo.


systematic_name: M3099
exact_source: GSE10463_1742_200_DN
source_species_code: HS
GEO_id: GSE10463
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of dendritic cells activated in the absense of VAF347 [PubChem=10172275] versus those activated in the presence of VAF347 [PubChem=10172275].

description_full:
  VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compound’s ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo.


systematic_name: M3100
exact_source: GSE10856_2033_200_UP
source_species_code: HS
GEO_id: GSE10856
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages treated with control (hIgG1) versus those treated with TNFRSF6B [GeneID=8771].

description_full:
  Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of lineages. DcR3 is capable of promoting angiogenesis, inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice over-expressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics.


systematic_name: M3101
exact_source: GSE10856_2033_200_DN
source_species_code: HS
GEO_id: GSE10856
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages treated with control (hIgG1) versus those treated with TNFRSF6B [GeneID=8771].

description_full:
  Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of lineages. DcR3 is capable of promoting angiogenesis, inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice over-expressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics.


description_brief: Genes up-regulated in comparison of naive T cells versus effector memory T cells.
systematic_name: M3104
exact_source: GSE11057_1610_200_UP
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples. Here we test the ability of this technique to determine the fractions of subsets of memory T cells in peripheral blood mononuclear cell (PBMC) samples.


systematic_name: M3110
exact_source: GSE11057_1612_200_DN
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of naive T cells versus peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3111
exact_source: GSE11057_1613_200_UP
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of effector memory T cells versus central memory T cells from peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3112
exact_source: GSE11057_1613_200_DN
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of effector memory T cells versus central memory T cells from peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3113
exact_source: GSE11057_1614_200_UP
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of effector memory T cells versus peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3114
exact_source: GSE11057_1614_200_DN
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comarison of effector memory T cells versus peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3116
exact_source: GSE11057_1615_200_UP
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of central memory T cells versus peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3117
exact_source: GSE11057_1615_200_DN
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of central memory T cells versus peripheral blood mononuclear cells (PBMC).

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3120
exact_source: GSE11057_1617_200_UP
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of peripheral mononuclear blood cells (PBMC) versus memory T cells.

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3121
exact_source: GSE11057_1617_200_DN
source_species_code: HS
GEO_id: GSE11057
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of peripheral mononuclear blood cells (PBMC) versus memory T cells.

description_full:
[cell repeats an earlier one in this file: 431 characters]


systematic_name: M3122
exact_source: GSE11864_1078_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435].

description_full:
  Gene expression analysis of freshly isolated CD14+ human monocytes and monocytes cultured in the presence or absence of interferon (IFN) -gamma for 24 h and then stimulated with Pam3Cys, a Toll-like receptor (TLR) 2 ligand, for 6 h. Results provide insight into mechanisms by which IFN-gamma reprograms early macrophage differentiation and subsequent response to TLR ligands.


systematic_name: M3123
exact_source: GSE11864_1078_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435].

description_full:
  Gene expression analysis of freshly isolated CD14+ human monocytes and monocytes cultured in the presence or absence of interferon (IFN) -gamma for 24 h and then stimulated with Pam3Cys, a Toll-like receptor (TLR) 2 ligand, for 6 h. Results provide insight into mechanisms by which IFN-gamma reprograms early macrophage differentiation and subsequent response to TLR ligands.


systematic_name: M3124
exact_source: GSE11864_1079_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458].

description_full:
  Gene expression analysis of freshly isolated CD14+ human monocytes and monocytes cultured in the presence or absence of interferon (IFN) -gamma for 24 h and then stimulated with Pam3Cys, a Toll-like receptor (TLR) 2 ligand, for 6 h. Results provide insight into mechanisms by which IFN-gamma reprograms early macrophage differentiation and subsequent response to TLR ligands.


systematic_name: M3127
exact_source: GSE11864_1079_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3129
exact_source: GSE11864_1080_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3130
exact_source: GSE11864_1080_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3131
exact_source: GSE11864_1081_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3132
exact_source: GSE11864_1081_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of untreated macrophages versus those cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3133
exact_source: GSE11864_1082_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3135
exact_source: GSE11864_1082_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3136
exact_source: GSE11864_1083_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3137
exact_source: GSE11864_1083_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF[GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3138
exact_source: GSE11864_1084_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3140
exact_source: GSE11864_1084_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3142
exact_source: GSE11864_1085_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458] versus macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3143
exact_source: GSE11864_1085_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458] versus macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3144
exact_source: GSE11864_1086_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458] versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3145
exact_source: GSE11864_1086_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and IFNG [GeneID=3458] versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cys (TLR2 agonist).

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3148
exact_source: GSE11864_1087_200_UP
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


systematic_name: M3149
exact_source: GSE11864_1087_200_DN
source_species_code: HS
GEO_id: GSE11864
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of macrophages cultured with M-CSF [GeneID=1435] and Pam3Cyc versus macrophages cultured with M-CSF [GeneID=1435], IFNG [GeneID=3458] and Pam3Cyc.

description_full:
[cell repeats an earlier one in this file: 375 characters]


description_brief: Genes up-regulated in comparison of T follicular helper (Tfh) cells versus Th1 cells.
systematic_name: M3151
exact_source: GSE11924_1088_200_UP
source_species_code: MM
GEO_id: GSE11924
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  After activation, CD4+ helper T (Th) cells differentiate into distinct effector subsets. Although chemokine (C-X-C motif) receptor 5-expressing T follicular helper (Tfh) cells are important in humoral immunity, their developmental regulation is unclear. Here we show that Tfh cells had a distinct gene expression profile and developed in vivo independently of the Th1 or Th2 cell lineages. Tfh cell generation was regulated by ICOS ligand (ICOSL) expressed on B cells and was dependent on interleukin-21 (IL-21), IL-6, and signal transducer and activator of transcription 3. However, unlike Th17 cells, differentiation of Tfh cells did not require transforming growth factor b (TGF-b) or Th17-specific orphan nuclear receptors RORa and RORg in vivo. Finally, naive T cells activated in vitro in the presence of IL-21 but not TGF-b signaling preferentially acquired Tfh gene expression and promoted germinal-center reactions in vivo. This study thus demonstrates that Tfh is a distinct Th cell lineage.


description_brief: Genes up-regulated in comparison of IgD+ B cells versus IgD- B cells.
systematic_name: M3182
exact_source: GSE12845_2019_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  B cells from human tonsil and blood were sorted using flow cytometry. The human samples were processed immediately ex-vivo using markers for known B cell subsets.


systematic_name: M3186
exact_source: GSE12845_2020_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of IgD+ peripheral blood B cells versus IgD- naive tonsil B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3187
exact_source: GSE12845_2021_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of IgD+ B cells from peripheral blood versus CD19 pre-germinal center tonsil B cell

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3188
exact_source: GSE12845_2021_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of IgD+ B cells from peripheral blood versus CD19 pre-germinal center tonsil B cell

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3189
exact_source: GSE12845_2022_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of IgD+ peripheral blood B cells versus dark zone germincal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3191
exact_source: GSE12845_2022_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of IgD+ peripheral blood B cells versus dark zone germincal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3192
exact_source: GSE12845_2023_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of IgD- peripheral blood B cells versus dark zone germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3193
exact_source: GSE12845_2023_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of IgD- peripheral blood B cells versus dark zone germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3194
exact_source: GSE12845_2024_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of IgD- peripheral blood B cells versus pre-germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3195
exact_source: GSE12845_2024_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of IgD- peripheral blood B cells versus pre-germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3203
exact_source: GSE12845_2028_200_UP
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of pre-germinal center B cells versus dark zone germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


systematic_name: M3204
exact_source: GSE12845_2028_200_DN
source_species_code: HS
GEO_id: GSE12845
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of pre-germinal center B cells versus dark zone germinal center B cells.

description_full:
[cell repeats an earlier one in this file: 162 characters]


description_brief: Genes up-regulated in comparison of immature NK cells versus mature NK cells.
systematic_name: M3205
exact_source: GSE13229_2029_200_UP
source_species_code: MM
GEO_id: GSE13229
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Previous reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development.


systematic_name: M3217
exact_source: GSE13306_1094_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of CD4 [GeneID=920] T cells activated with lamina propria dendritic cells versus regulatory T cell (Treg).

description_full:
  CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.


systematic_name: M3219
exact_source: GSE13306_1094_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] T cells activated with lamina propria dendritic cells versus regulatory T cell (Treg).

description_full:
  CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.


systematic_name: M3220
exact_source: GSE13306_1095_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of regulatory T cell (Treg) versus conventional T cells activated with lamina propria dendritic cells.

description_full:
  CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.


systematic_name: M3222
exact_source: GSE13306_1095_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of regulatory T cell (Treg) versus conventional T cells activated with lamina propria dendritic cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3226
exact_source: GSE13306_1097_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in regulatory T cell (Treg) treated with retinoic acid (tretinoin) [PubChem=444795] versus conventional T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3227
exact_source: GSE13306_1097_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in regulatory T cell (Treg) treated with retinoic acid (tretinoin) [PubChem=444795] versus conventional T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3232
exact_source: GSE13306_1099_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of regulatory T cell (Treg) treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3233
exact_source: GSE13306_1099_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of regulatory T cell (Treg) treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3234
exact_source: GSE13306_1100_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of conventional T cells treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated conventional T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3235
exact_source: GSE13306_1100_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of conventional T cells treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated conventional T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3236
exact_source: GSE13306_1101_200_UP
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of memory CD4 [GeneID=920] T cells treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated memory CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


systematic_name: M3237
exact_source: GSE13306_1101_200_DN
source_species_code: MM
GEO_id: GSE13306
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of memory CD4 [GeneID=920] T cells treated with retinoic acid (tretinoin) [PubChem=444795] versus untreated memory CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 1031 characters]


description_brief: Genes up-regulated in comparison of naive B cells versus IgM-memory B cells.
systematic_name: M3239
exact_source: GSE13411_1618_200_UP
source_species_code: HS
GEO_id: GSE13411
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of naive and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than naïve B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not naïve B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool.


systematic_name: M3257
exact_source: GSE13484_2209_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 0 h  versus PBMC cultured for 3 h with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 11,639 genes in PBMCs from 2 donors cultured with YF-17D vaccine were accessed after 3 and 12 hours.


systematic_name: M3260
exact_source: GSE13484_2209_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 0 h  versus PBMC cultured for 3 h with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 11,639 genes in PBMCs from 2 donors cultured with YF-17D vaccine were accessed after 3 and 12 hours.


systematic_name: M3262
exact_source: GSE13484_2210_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 0 h versus PBMC cultured for 12 h with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 11,639 genes in PBMCs from 2 donors cultured with YF-17D vaccine were accessed after 3 and 12 hours.


systematic_name: M3264
exact_source: GSE13484_2210_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 0 h versus PBMC cultured for 12 h with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3266
exact_source: GSE13484_2211_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 3 h versus PBMC cultured for 3 h with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3267
exact_source: GSE13484_2211_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 3 h versus PBMC cultured for 3 h with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3271
exact_source: GSE13484_2212_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 12 h versus PBMC cultured for 12 h with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3273
exact_source: GSE13484_2212_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) cultured for 12 h versus PBMC cultured for 12 h with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3275
exact_source: GSE13484_2213_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of peripheral blood mononuclear cells (PBMC) cultured with YF17D vaccine for 12 h versus PBMC cultured for 3 h.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3276
exact_source: GSE13484_2213_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of peripheral blood mononuclear cells (PBMC) cultured with YF17D vaccine for 12 h versus PBMC cultured for 3 h.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3277
exact_source: GSE13484_2214_200_UP
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC stimulated with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3279
exact_source: GSE13484_2214_200_DN
source_species_code: HS
GEO_id: GSE13484
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC stimulated with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 154 characters]


systematic_name: M3280
exact_source: GSE13485_2215_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 1 day after stimulation with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.


systematic_name: M3281
exact_source: GSE13485_2215_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 1 day after stimulation with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.


systematic_name: M3282
exact_source: GSE13485_2216_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 3 days after stimulation with YF17D vaccine.

description_full:
  The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.


systematic_name: M3286
exact_source: GSE13485_2216_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 3 days after stimulation with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3287
exact_source: GSE13485_2217_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 7 days after stimulation with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3288
exact_source: GSE13485_2217_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 7 days after stimulation with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3289
exact_source: GSE13485_2218_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 21 days after stimulation with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3290
exact_source: GSE13485_2218_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) versus PBMC 21 days after stimulation with YF17D vaccine.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3291
exact_source: GSE13485_2219_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 3 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3294
exact_source: GSE13485_2219_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 3 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3295
exact_source: GSE13485_2220_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 7 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3296
exact_source: GSE13485_2220_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 7 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3298
exact_source: GSE13485_2221_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3299
exact_source: GSE13485_2221_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 1 day after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3300
exact_source: GSE13485_2222_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 3 days after stimulation with YF17D vaccine versus PBMC 7 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3302
exact_source: GSE13485_2222_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 3 days after stimulation with YF17D vaccine versus PBMC 7 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3303
exact_source: GSE13485_2223_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 3 days after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3306
exact_source: GSE13485_2223_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 3 days after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3307
exact_source: GSE13485_2224_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 7 days after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3308
exact_source: GSE13485_2224_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of unstimulated peripheral blood mononuclear cells (PBMC) 7 days after stimulation with YF17D vaccine versus PBMC 21 days after the stimulation.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3310
exact_source: GSE13485_2225_200_UP
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of peripheral blood mononuclear cells (PBMC) before vs after YF17D vaccination.

description_full:
[cell repeats an earlier one in this file: 369 characters]


systematic_name: M3311
exact_source: GSE13485_2225_200_DN
source_species_code: HS
GEO_id: GSE13485
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of peripheral blood mononuclear cells (PBMC) before vs after YF17D vaccination.


systematic_name: M3312
exact_source: GSE13493_1525_200_UP
source_species_code: MM
GEO_id: GSE13493
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes versus CD4 [GeneID=920] Int CD8 thymocytes.

description_full:
  T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection. We used microarrays to identify the genes differentially expressed during CD8 single positive T cell development in N15 TCR transgenic Rag2 deficient mice.


systematic_name: M3313
exact_source: GSE13493_1525_200_DN
source_species_code: MM
GEO_id: GSE13493
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes versus CD4 [GeneID=920] Int CD8 thymocytes.

description_full:
  T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection. We used microarrays to identify the genes differentially expressed during CD8 single positive T cell development in N15 TCR transgenic Rag2 deficient mice.


systematic_name: M3319
exact_source: GSE13738_1725_200_UP
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of resting CD4 [GeneID=920] T cells versus directly activated CD4 [GeneID=920] T cells.

description_full:
  There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of ‘bystander’ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.


systematic_name: M3320
exact_source: GSE13738_1725_200_DN
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of resting CD4 [GeneID=920] T cells versus directly activated CD4 [GeneID=920] T cells.

description_full:
  There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of ‘bystander’ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.


systematic_name: M3321
exact_source: GSE13738_1726_200_UP
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of resting CD4 [GeneID=920] T cells versus bystander activated CD4 [GeneID=920] T cells.

description_full:
  There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of ‘bystander’ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.


systematic_name: M3322
exact_source: GSE13738_1726_200_DN
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of resting CD4 [GeneID=920] T cells versus bystander activated CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 1094 characters]


systematic_name: M3324
exact_source: GSE13738_1727_200_UP
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of directly activated CD4 [GeneID=920] T cells versus bystander activated CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 1094 characters]


systematic_name: M3325
exact_source: GSE13738_1727_200_DN
source_species_code: HS
GEO_id: GSE13738
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of directly activated CD4 [GeneID=920] T cells versus bystander activated CD4 [GeneID=920] T cells.

description_full:
[cell repeats an earlier one in this file: 1094 characters]


systematic_name: M3326
exact_source: GSE14000_1528_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA versus total mRNA in dendritic cells.

description_full:
  Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.


systematic_name: M3327
exact_source: GSE14000_1528_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA versus total mRNA in dendritic cells.

description_full:
  Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.


systematic_name: M3328
exact_source: GSE14000_1529_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA versus total mRNA 4 h after LPS (TLR4 agonist) stimulation.

description_full:
  Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.


systematic_name: M3329
exact_source: GSE14000_1529_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA versus total mRNA 4 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3332
exact_source: GSE14000_1530_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA versus total mRNA 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3333
exact_source: GSE14000_1530_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA versus total mRNA 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3337
exact_source: GSE14000_1531_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA before and 4 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3338
exact_source: GSE14000_1531_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA before and 4 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3343
exact_source: GSE14000_1532_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA before and 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3344
exact_source: GSE14000_1532_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA before and 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3345
exact_source: GSE14000_1533_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of dendritic cells (DC) before and 4 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3347
exact_source: GSE14000_1533_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of dendritic cells (DC) before and 4 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3348
exact_source: GSE14000_1534_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of dendritic cells (DC) before and 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3350
exact_source: GSE14000_1534_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of dendritic cells (DC) before and 16 h after LPS (TLR4 agonist) stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3351
exact_source: GSE14000_1535_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of polysome bound (translated) mRNA in dendritic cells (DC) at 4 h after LPS (TLR4 agonist) stimulation versus those at 16 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3352
exact_source: GSE14000_1535_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of polysome bound (translated) mRNA in dendritic cells (DC) at 4 h after LPS (TLR4 agonist) stimulation versus those at 16 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3354
exact_source: GSE14000_1536_200_UP
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of dendritic cells (DC) at 4 h after LPS (TLR4 agonist) stimulation versus those at 16 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


systematic_name: M3355
exact_source: GSE14000_1536_200_DN
source_species_code: HS
GEO_id: GSE14000
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of dendritic cells (DC) at 4 h after LPS (TLR4 agonist) stimulation versus those at 16 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 1519 characters]


description_brief: Genes up-regulated in comparison of Th2 cells versus Th1 cells.
systematic_name: M3359
exact_source: GSE14308_1103_200_UP
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Multipotential naïve CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naïve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation.


systematic_name: M3391
exact_source: GSE14308_1115_200_UP
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of naive CD4 [GeneID=920] T cells versus induced regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3392
exact_source: GSE14308_1115_200_DN
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of naive CD4 [GeneID=920] T cells versus induced regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3393
exact_source: GSE14308_1116_200_UP
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of naive CD4 [GeneID=920] T cells versus natural regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3394
exact_source: GSE14308_1116_200_DN
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of naive CD4 [GeneID=920] T cells versus natural regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3396
exact_source: GSE14308_1117_200_UP
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of induced regulatory T cell (Treg) versus natural regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3399
exact_source: GSE14308_1117_200_DN
source_species_code: MM
GEO_id: GSE14308
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of induced regulatory T cell (Treg) versus natural regulatory T cell (Treg).

description_full:
[cell repeats an earlier one in this file: 1038 characters]


systematic_name: M3400
exact_source: GSE1432_1753_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of control microglia cells versus those 1 h after stimulation with IFNG [GeneID=3458].

description_full:
  Microglial cells are resident macrophages in the central nervous system (CNS) and play a pivotal role in the innate and adaptive immune responses against microbial infections. The immune functions of microglia are regulated by a milieu of cytokines including interferon (IFN)-gamma. We here performed a series of experiments to acertain the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. Primary human microglial cells were either untreated or treated with 200u/ml IFN-gamma. Affymetrix U133A chips were utilized. Four different tissue samples (B18, O, W, and Y20) were analyzed at the three time points.


systematic_name: M3401
exact_source: GSE1432_1753_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of control microglia cells versus those 1 h after stimulation with IFNG [GeneID=3458].

description_full:
  Microglial cells are resident macrophages in the central nervous system (CNS) and play a pivotal role in the innate and adaptive immune responses against microbial infections. The immune functions of microglia are regulated by a milieu of cytokines including interferon (IFN)-gamma. We here performed a series of experiments to acertain the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. Primary human microglial cells were either untreated or treated with 200u/ml IFN-gamma. Affymetrix U133A chips were utilized. Four different tissue samples (B18, O, W, and Y20) were analyzed at the three time points.


systematic_name: M3404
exact_source: GSE1432_1754_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of control microglia cells versus those 6 h after stimulation with IFNG [GeneID=3458].

description_full:
  Microglial cells are resident macrophages in the central nervous system (CNS) and play a pivotal role in the innate and adaptive immune responses against microbial infections. The immune functions of microglia are regulated by a milieu of cytokines including interferon (IFN)-gamma. We here performed a series of experiments to acertain the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. Primary human microglial cells were either untreated or treated with 200u/ml IFN-gamma. Affymetrix U133A chips were utilized. Four different tissue samples (B18, O, W, and Y20) were analyzed at the three time points.


systematic_name: M3405
exact_source: GSE1432_1754_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of control microglia cells versus those 6 h after stimulation with IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3407
exact_source: GSE1432_1755_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of control microglia cells versus those 24 h after stimulation with IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3408
exact_source: GSE1432_1755_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of control microglia cells versus those 24 h after stimulation with IFNG [GeneID=3458].

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3409
exact_source: GSE1432_1756_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of microglia cells 1 h after stimulation with IFNG [GeneID=3458] versus microglia cells 6 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3411
exact_source: GSE1432_1756_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of microglia cells 1 h after stimulation with IFNG [GeneID=3458] versus microglia cells 6 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3413
exact_source: GSE1432_1757_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of microglia cells 1 h after stimulation with IFNG [GeneID=3458] versus microglia cells 24 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3414
exact_source: GSE1432_1757_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of microglia cells 1 h after stimulation with IFNG [GeneID=3458] versus microglia cells 24 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3415
exact_source: GSE1432_1758_200_UP
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of microglia cells 6 h after stimulation with IFNG [GeneID=3458] versus microglia cells 24 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


systematic_name: M3416
exact_source: GSE1432_1758_200_DN
source_species_code: HS
GEO_id: GSE1432
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of microglia cells 6 h after stimulation with IFNG [GeneID=3458] versus microglia cells 24 h after the stimulation.

description_full:
[cell repeats an earlier one in this file: 658 characters]


description_brief: Genes up-regulated in comparison of regulatory T cell (Treg) versus effector T cells.
systematic_name: M3417
exact_source: GSE14350_1118_200_UP
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here we show that expression of IL-2Rbeta chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rbeta-deficient mice resulted in production of a normal proportion of natural Treg cells that suppressed severe autoimmunity related with deficiency in IL-2 or IL-2R. These mutant IL-2Rbeta chains supported suboptimal and transient STAT5 activation that upregulate the transcription factor Foxp3 to normal amounts in natural, but not induced, Treg cells. Using cells T cell obtained from normal C57BL/6 mice and mice harboring Treg cells with impaired IL-2R signaling, gene expression profiling revealed many targets in peripheral natural Treg cells that were IL-2-dependent and a substantial overlap between the Treg cell IL-2-dependent gene program and the Treg cell transcriptional signature. Collectively, these findings demonstrate that a critical, and perhaps minor, subset of IL-2-dependent targets in Treg cells is indexed to a low IL-2R signaling threshold and that a substantial proportion of the Treg cell gene program is regulated by IL-2. CD4 T effector cells also showed many IL-2R-dependent gene and these also overlapped in a distintive manner with the IL-2-dependent genes of Treg cells and the Treg gene signature.


systematic_name: M3419
exact_source: GSE14350_1119_200_UP
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of regulatory T cell (Treg) from IL2RB [GeneID=3560] defficient mice versus effector T cells from IL2RB [GeneID=3560] defficient mice.

description_full:
  Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here we show that expression of IL-2Rbeta chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rbeta-deficient mice resulted in production of a normal proportion of natural Treg cells that suppressed severe autoimmunity related with deficiency in IL-2 or IL-2R. These mutant IL-2Rbeta chains supported suboptimal and transient STAT5 activation that upregulate the transcription factor Foxp3 to normal amounts in natural, but not induced, Treg cells. Using cells T cell obtained from normal C57BL/6 mice and mice harboring Treg cells with impaired IL-2R signaling, gene expression profiling revealed many targets in peripheral natural Treg cells that were IL-2-dependent and a substantial overlap between the Treg cell IL-2-dependent gene program and the Treg cell transcriptional signature. Collectively, these findings demonstrate that a critical, and perhaps minor, subset of IL-2-dependent targets in Treg cells is indexed to a low IL-2R signaling threshold and that a substantial proportion of the Treg cell gene program is regulated by IL-2. CD4 T effector cells also showed many IL-2R-dependent gene and these also overlapped in a distintive manner with the IL-2-dependent genes of Treg cells and the Treg gene signature.


systematic_name: M3420
exact_source: GSE14350_1119_200_DN
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of regulatory T cell (Treg) from IL2RB [GeneID=3560] defficient mice versus effector T cells from IL2RB [GeneID=3560] defficient mice.

description_full:
[cell repeats an earlier one in this file: 1412 characters]


systematic_name: M3421
exact_source: GSE14350_1120_200_UP
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of regulatory T cell (Treg) from IL2RB [GeneID=3560] defficient mice versus regulatory T cell (Treg) from wild type animals.

description_full:
[cell repeats an earlier one in this file: 1412 characters]


systematic_name: M3422
exact_source: GSE14350_1120_200_DN
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of regulatory T cell (Treg) from IL2RB [GeneID=3560] defficient mice versus regulatory T cell (Treg) from wild type animals.

description_full:
[cell repeats an earlier one in this file: 1412 characters]


systematic_name: M3423
exact_source: GSE14350_1121_200_UP
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of effector T cells from IL2RB [GeneID=3560] defficient mice versus effector T cells from wild type animals.

description_full:
[cell repeats an earlier one in this file: 1412 characters]


systematic_name: M3424
exact_source: GSE14350_1121_200_DN
source_species_code: MM
GEO_id: GSE14350
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of effector T cells from IL2RB [GeneID=3560] defficient mice versus effector T cells from wild type animals.

description_full:
[cell repeats an earlier one in this file: 1412 characters]


systematic_name: M3425
exact_source: GSE1448_2130_200_UP
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of control CD4 [GeneID=920] CD8 thymocytes versus those after stimulation with anti-Valpha2 antibodies.

description_full:
  Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies


systematic_name: M3426
exact_source: GSE1448_2130_200_DN
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of control CD4 [GeneID=920] CD8 thymocytes versus those after stimulation with anti-Valpha2 antibodies.

description_full:
  Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies


systematic_name: M3428
exact_source: GSE1448_2131_200_UP
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of control CD4 [GeneID=920] CD8 thymocytes versus those after stimulation with anti-Vbeta5 antibodies.

description_full:
  Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies


systematic_name: M3429
exact_source: GSE1448_2131_200_DN
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of control CD4 [GeneID=920] CD8 thymocytes versus those after stimulation with anti-Vbeta5 antibodies.

description_full:
[cell repeats an earlier one in this file: 125 characters]


systematic_name: M3431
exact_source: GSE1448_2132_200_UP
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes stimulated with anti-Valpha2 antibodies versus CD4 [GeneID=920] CD8 thymocytes stimulated with anti-beta5 antibodies.

description_full:
[cell repeats an earlier one in this file: 125 characters]


systematic_name: M3435
exact_source: GSE1448_2132_200_DN
source_species_code: MM
GEO_id: GSE1448
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes stimulated with anti-Valpha2 antibodies versus CD4 [GeneID=920] CD8 thymocytes stimulated with anti-beta5 antibodies.

description_full:
[cell repeats an earlier one in this file: 125 characters]


systematic_name: M3436
exact_source: GSE1460_2133_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of intrathymic T progenitor cells (ITTP) versus CD4 [GeneID=920] CD8 thymocytes.

description_full:
  Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ \double positive\ thymocytes (DP), CD3highCD4+CD8- \single positive\ thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from adult blood (AB4+).


systematic_name: M3438
exact_source: GSE1460_2133_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of intrathymic T progenitor cells (ITTP) versus CD4 [GeneID=920] CD8 thymocytes.

description_full:
  Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ \double positive\ thymocytes (DP), CD3highCD4+CD8- \single positive\ thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from adult blood (AB4+).


systematic_name: M3439
exact_source: GSE1460_2134_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of intrathymic T progenitor cells (ITTP) versus CD4 [GeneID=920] thymocytes.

description_full:
  Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ \double positive\ thymocytes (DP), CD3highCD4+CD8- \single positive\ thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naive T cells from adult blood (AB4+).


systematic_name: M3440
exact_source: GSE1460_2134_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of intrathymic T progenitor cells (ITTP) versus CD4 [GeneID=920] thymocytes.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3441
exact_source: GSE1460_2135_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of intrathymic T progenitor cells (ITTP) versus naive CD4 [GeneID=920] T cells from cord blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3445
exact_source: GSE1460_2135_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of intrathymic T progenitor cells (ITTP) versus naive CD4 [GeneID=920] T cells from cord blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3446
exact_source: GSE1460_2136_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of intrathymic T progenitor cells (ITTP) versus naive CD4 [GeneID=920] T cells from adult blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3448
exact_source: GSE1460_2136_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of intrathymic T progenitor cells (ITTP) versus naive CD4 [GeneID=920] T cells from adult blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3449
exact_source: GSE1460_2137_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of intrathymic T progenitor cells (ITTP) versus thymic stromal cells.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3450
exact_source: GSE1460_2137_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of intrathymic T progenitor cells (ITTP) versus thymic stromal cells.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3454
exact_source: GSE1460_2138_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes versus T cells from cord blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3459
exact_source: GSE1460_2139_200_UP
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes versus naive CD4 [GeneID=920] T cells from cord blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


systematic_name: M3460
exact_source: GSE1460_2139_200_DN
source_species_code: HS
GEO_id: GSE1460
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in comparison of CD4 [GeneID=920] CD8 thymocytes versus naive CD4 [GeneID=920] T cells from cord blood.

description_full:
[cell repeats an earlier one in this file: 402 characters]


