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GSE30356
Mus musculus
4 Downloadable Samples
Description
Endothelin-1 (ET-1) plays a critical role in connective tissue remodeling by fibroblasts during tissue repair and fibrosis. We investigated the molecular pathways in the transmission of ET-1 signals that lead to features of connective tissue remodeling, in particular the role of FAK (focal adhesion kinase).
Publication Title
Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation.
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Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Wnt9b is expressed in the ureteric bud of the kidney at all stages of development. In Wnt9b mutants, the ureteric bud forms but the metanephric mesenchyme is never induced to undergo differentiation.
Publication Title
Myc cooperates with β-catenin to drive gene expression in nephron progenitor cells.
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Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
Publication Title
SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.
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Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Publication Title
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
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Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 39 Downloadable Samples
Description
Genomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant’s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.
Publication Title
Hepatic gene expression profiling using Genechips in zebrafish exposed to 17alpha-ethynylestradiol.
Alternate Accession IDs
None
Sample Metadata Fields
Sex, Specimen part, Compound, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray
Publication Title
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
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Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Activated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis.
Publication Title
FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
Description
Ikaros family DNA binding proteins are critical regulators of B cell development. To identify Ikaros-regulated genes in pre-B cells we performed gene expression studies at enhanced temporal resolution.
Publication Title
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Comparative analysis of cerebellar gene expression changes occurring in Sca1154Q/2Q and Sca7266Q/5Q knock-in mice
Publication Title
The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7.
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Sample Metadata Fields
Sex, Age
View Samples