C3H10T1/2 stem cells are committed to the adipocyte lineage by treatment with BMP-4 and grown to postconfluence. When subjected to our standard differentiation protocol, the committed cells differentiate into adipocytes in a manner indistinguishable from that of 3T3-L1 preadipocytes. In contrast, C3H10T1/2 cells not committed with BMP-4 remain undifferentiated despite treatment with differentiation inducers. The molecular basis of the commitment process, however, has not been elucidated. Since postconfluent uncommitted and committed C3H10T1/2 cells respond differently to the differentiation inducers, it was reasoned that the two cell types differed at the gene expression level. Therefore, we undertook microarray gene expression profiling to detect changes between the two cell populations at postconfluence to identify expressed genes that may be responsible for the dramatic change in phenotype.
BMP-4 treatment of C3H10T1/2 stem cells blocks expression of MMP-3 and MMP-13.
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View SamplesDifferential expression patterns of total mRNA in traditionally expanded T cells (vehicle) compared to T cells expanded under drugs (AKT inhibitor and CAL-101) Overall design: Comparison of transcriptional effects of two different drugs
PI3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8<sup>+</sup> T Cells.
Specimen part, Treatment, Subject
View SamplesEpigenetic events, including covalent post-translational modification of histones, have frequently been demonstrated to play critical roles in tumor development and progression. The transcriptional coactivator, p300/CBP, possesses both histone acetyltransferase (HAT) activity as well as scaffolding properties that directly influence transcriptional activation of targeted genes. We have used a recently reported small molecule inhibitor of p300 HAT activity, C646, to explore the specific contribution of p300/CBP HAT activity to tumor development and progression. We find that C646 inhibits the growth of lineage-specific tumor cell lines including human melanomas through direct transcriptional regulation of cell cycle regulatory proteins. Further evaluation of the p300 HAT transcriptome in human melanoma cells using comprehensive gene expression profiling reveals that p300 HAT activity globally promotes cell cycle progression, nucleosome assembly, and the DNA damage checkpoint through direct transcriptional regulatory mechanisms. Additionally, C646 promotes sensitivity to DNA damaging agents leading to enhanced apoptosis of melanoma cells following combination treatment with cisplatin. Together our data suggest that p300 HAT activity regulates critical growth regulatory pathways in tumors and may serve as a novel therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents.
Selective inhibition of p300 HAT blocks cell cycle progression, induces cellular senescence, and inhibits the DNA damage response in melanoma cells.
Cell line, Treatment, Time
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MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
Sex, Age, Race
View SamplesmRNA expression was assayed from bronchial epithelial cells collected via bronchoscopy from healthy current and never smoker volunteers in order to determine relationships between microRNA and mRNA expression in bronchial epithelial cell samples across current and never smokers and within the same individual.
MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
Sex, Age, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming.
Sex, Specimen part
View SamplesKaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The effects of KSHV infection of both LEC and BEC were assayed using Affymetrix hgu133plus2 chips at 72 hours post infection.
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming.
Specimen part
View SamplesKaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple microRNA in a single cluster. Here we test the effects of this KSHV microRNA cluster in LEC cells using Affymetrix hgu133plus2 chips.
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming.
Specimen part
View SamplesKaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple MAF-downregulating microRNA. Here we test the effects of MAF silencing by siRNA in LEC cells using Affymetrix hgu133plus2 chips.
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming.
Specimen part
View SamplesFlaviviruses, particularly Japanese encephalitis virus (JEV) and West Nile virus (WNV), are important causes of virus-induced central nervous system (CNS) disease in humans. We used microarray analysis to identify cellular genes that are differentially regulated following infection of the brain with JEV (P3) or WNV (New York 99). Gene expression data for these flaviviruses was compared to that induced following infection of the brain with reovirus (Type 3 Dearing), an unrelated neurotropic virus. Although several studies have described gene expression changes following virus infection of the brain, this report is the first to directly compare large-scale gene expression data from different viruses. We found that a large number of genes were up-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001), including genes associated with interferon signaling, the immune system, inflammation and cell death/survival signaling. In addition, genes associated with glutamate signaling were down-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001). These genes may serve broad spectrum therapeutic targets for virus-induced CNS disease. A distinct set of genes were up-regulated following flavivirus-infection, but not following infection with reovirus. These genes were associated with tRNA charging and may serve as therapeutic targets for flavivirus-induce CNS disease.
Virus-induced transcriptional changes in the brain include the differential expression of genes associated with interferon, apoptosis, interleukin 17 receptor A, and glutamate signaling as well as flavivirus-specific upregulation of tRNA synthetases.
Specimen part, Treatment
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