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GSE9927
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection.
Publication Title
Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 162 Downloadable Samples
IlluminaHiSeq2500
Description
Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming, we treated zebrafish embryos with cortisol and examined the effects on adults. In adulthood, the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity. Overall design: 30 samples total were analyzed. 9 caudal fins samples (0, 2 and 4dpa), 3 blood samples and 3 muscle samples from adults exposed to DMSO control as embryos. 9 caudal fins samples (0, 2 and 4dpa), 3 blood samples and 3 muscle samples from adults exposed to cortisol (1 micromolar) as embryos.
Publication Title
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to characterize gene expression networks linked to AT1 angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1A receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. At baseline, 405 genes were differentially expressed (>1.5X) between WT and KO kidneys. Of these, more than 80% were up-regulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ~805 genes was altered (18% up-regulated, 82% repressed). Genes in metabolism and ion transport pathways were up-regulated while there was attenuated expression of protective genes against oxidative stress including glutathione synthetase and mitochondrial SOD2. Angiotensin II infusion has little effect on blood pressure in KOs. Nonetheless, expression of more than 250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were up-regulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation.
Publication Title
Gene expression profiles linked to AT1 angiotensin receptors in the kidney.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with 1 micromolar cortisol and examined the effects on larvae. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and up-regulated genes associated with defense response and immune system processes. Overall design: 6 samples total were analyzed. 3 DMSO controls, and 3 cortisol treated (1 micromolar).
Publication Title
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53 and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell cycle arrest, apoptosis, and p53-target gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.
Publication Title
The WTX tumor suppressor enhances p53 acetylation by CBP/p300.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 16 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors repressed FOXO.
Publication Title
The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
Publication Title
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The human SYT-SSX fusion protein was expressed in a developmentally dependent fashion in murine myoblasts. Tumors harvested from mice in adolescence were compared to normal mouse skeletal muscle samples.
Publication Title
A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
Publication Title
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples