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GSE5921
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
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.
Publication Title
BMP-4 treatment of C3H10T1/2 stem cells blocks expression of MMP-3 and MMP-13.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Flaviviruses, 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.
Publication Title
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.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Increasing evidence supports the existence of a subpopulation of cancer cells capable of self-renewal and differentiation into diverse cell lineages. These cancer stem-like or cancer-initiating cells (CICs) also demonstrate resistance to chemo- and radiotherapy and may function as a primary source of cancer recurrence. We report here on the isolation and in vitro propagation of multicellular ovarian cancer spheroids from a well-established ovarian cancer cell line (OVCAR-3). The spheroid-derived cells (SDCs) display self-renewal potential, the ability to produce differentiated progeny, and increased expression of genes previously associated with CICs. SDCs also demonstrate higher invasiveness, migration potential, and enhanced resistance to standard anticancer agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transition (EMT), anticancer drug resistance and/or decreased susceptibility to apoptosis, as well as, down-regulation of genes typically associated with the epithelial cell phenotype and pro-apoptotic genes. Pathway and biological process enrichment analyses indicate significant differences between the SDCs and precursor OVCAR-3 cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism, NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs will be a useful model for the study of ovarian CICs and for the development of novel CIC-targeted therapies.
Publication Title
Isolation and characterization of stem-like cells from a human ovarian cancer cell line.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 4000
Description
In many forms of retinal degenerative diseases in human, microglia relocate to and accumulate in the subretinal space. However, the roles of microglia in retinal degeneration are poorly understood. By leveraging single cell RNA-seq, we identified a distinct microglia subtype in the subretinal space. These microglia underwent transcriptional reprogramming characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. Importantly, this transition is associated with protection of the retinal pigment epithelium from damage caused by disease. Therefore, our data demonstrated microglial heterogeneity in retinal degeneration and may provide important implications for developing new strategies to prevent loss of vision. Overall design: Transcriptional profiling of Cx3cr1+ single cells from the mouse model of light-induced retinal degeneration with matched control, generated from single cell RNA-sequencing of over 10,000 cells.
Publication Title
Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The regional specificity and timing of gene activation following chemotherapy, and how this relates to subsequent mucositis development is currently unknown. The aim of the study was therefore to determine the early time course of gene expression changes along the gastrointestinal tract (GIT) of the DA rat following irinotecan treatment, so as to provide an insight into the genetic component of mucositis.
Publication Title
Gene expression analysis of multiple gastrointestinal regions reveals activation of common cell regulatory pathways following cytotoxic chemotherapy.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. Nine metabolites predicted to be lowered in Jurkat cells with respect to normal lymphoblasts were examined: riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, -hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole. All, alone or in combination, exhibited antiproliferative activity. Of eleven metabolites predicted to be increased or unchanged in Jurkat cells, only two (bilirubin and androsterone) exhibited significant antiproliferative activity. These results suggest that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, resulting in uninhibited cellular growth and have the implication that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery.
Publication Title
Identification of metabolites with anticancer properties by computational metabolomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion.
Publication Title
LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted mRNAs making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted messenger RNAs (mRNAs) were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ~6-11% of predicted target mRNAs. Our results underscore the complexities of miRNA-mediated regulation in vivo and caution against the widespread clinical application of miRNAs and miRNA inhibitors until the basis of these complexities is more fully understood.
Publication Title
Evidence for the complexity of microRNA-mediated regulation in ovarian cancer: a systems approach.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In contrast to epithelial derived carcinomas that arise in most human organs, ovarian surface epithelial cells become more rather than less differentiated as the malignancy progresses. To test the hypothesis that ovarian surface epithelial cells retain properties of relatively uncommitted pluripotent cells until undergoing neoplastic transformation, we conducted gene expression profiling analysis (Affymetrix, U133 Plus 2.0) of 12 ovarian surface epithelial cells and 12 laser capture microdissected serous papillary ovarian cances. We find that over 2000 genes are significantly differentially expressed between the surface epithelial and cancer samples. Network analysis implicates key signaling pathways and pathway interactions in ovarian cancer development. Genes previously associated with adult stem cell maintenance are expressed in ovarian surface epithelial cells and significantly down-regulated in ovarian cancer cells. Our results indicate that the surface of the ovary is an adult stem cell niche and that deregulation of genes involved in maintaining the quiescence of ovarian surface epithelial cells is instrumental in the initiation and development of ovarian cancer.
Publication Title
Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TCPOBOP (1,4-Bis [2-(3,5-Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP-induced direct hyperplasia has been considered to be CAR-dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and EGFR, are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP-induced direct hyperplasia, not yet explored, is investigated in the current study. Disruption of the RTK-mediated signaling was achieved utilizing MET KO mice along with Canertinib treatment for EGFR inhibition. Combined elimination of MET and EGFR signaling [MET KO + EGFRi], but not individual disruption, dramatically reduced TCPOBOP-induced hepatomegaly and hepatocyte proliferation. TCPOBOP-driven CAR activation was not altered in [MET KO + EGFRi] mice, as measured by nuclear CAR translocation and analysis of typical CAR target genes. However, TCPOBOP induced cell cycle activation was impaired in [MET KO + EGFRi] mice due to defective induction of cyclins, which regulate cell cycle initiation and progression. TCPOBOP-driven induction of FOXM1, a key transcriptional regulator of cell cycle progression during TCPOBOP-mediated hepatocyte proliferation, was greatly attenuated in [MET KO + EGFRi] mice. Interestingly, TCPOBOP treatment caused transient decline in HNF4 expression concomitant to proliferative response; this was not seen in [MET KO + EGFRi] mice. Transcriptomic profiling revealed vast majority (~40%) of TCPOBOP-dependent genes mainly related to proliferative response, but not to drug metabolism, were differentially expressed in [MET KO + EGFRi] mice. Conclusion: Taken together, combined disruption of EGFR and MET signaling lead to dramatic impairment of TCPOBOP-induced proliferative response without altering CAR activation.
Publication Title
TCPOBOP-induced hepatomegaly &amp; hepatocyte proliferation is attenuated by combined disruption of MET &amp; EGFR signaling.
Sample Metadata Fields
No sample metadata fields
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