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SRP141017
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2000
Description
Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2a, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2a by Notch under normoxic conditions leads to elevated HIF2a protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma and renal cell carcinoma cell lines. The elevated level of HIF2a protein was in certain tumor cell types accompanied by down-regulation of HIF1a protein levels, indicating that high Notch signaling may drive a HIF1a-to-HIF2a switch. At the transcriptome level, the presence of HIF2a was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2a expression was knocked down by HIF2a siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2a, which may be important for future cancer therapies. Overall design: DAOY-NERT2 cells, +/- Notch induction by Tamoxifen (TMX) for 48 hours, +/- hypoxia (1% O2) treatment for 48 hours, where HIF1a or HIF2a had been knocked down by siRNA, were subjected to RNA sequencing. The quality of the cDNA libraries was tested on an Agilent 2100 bioanalyzer. The libraries were sequenced on an Illumina HiSeq 2000 system, and the reads were aligned to the human genome (assembly hg19) and a transcriptome database (RefSeq and Ensembl) using bowtie. RPKM values were generated using rpkmforgenes.
Publication Title
Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression analysis from two genetically engineered mouse models of osteosarcoma determine the expression profile of mouse osteosarcoma Human osteosarcoma (OS) is comprised of three different subtypes: fibroblastic, chondroblastic and osteoblastic. We previously generated a mouse model of fibroblastic OS by conditional deletion of p53 and Rb in osteoblasts. Here we report an accurate mouse model of the osteoblastic subtype using shRNA-based suppression of p53. Like human OS, tumors frequently present in the long bones and preferentially disseminate to the lungs; features less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using different technology. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of a distinct clinical subtype of OS that was not previously represented and more fully recapitulated the clinical spectrum of this human tumor.
Publication Title
Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and peripheral blood mononuclear cells.
Publication Title
Two-way learning with one-way supervision for gene expression data.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and peripheral blood mononuclear cells.
Publication Title
Two-way learning with one-way supervision for gene expression data.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and whole blood.
Publication Title
Two-way learning with one-way supervision for gene expression data.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Mitochondrial biogenesis is regulated by signaling pathways sensitive to extracellular conditions and to the internal environment of the cell. We found that deletion of protein phosphatase 2A (PP2A) or of protein phosphatase 6 (PP6) diminishes the nuclear transcriptional response associated with mtDNA damage. Overall design: Six samples were analyzed to determine message RNA levels.
Publication Title
Deletion of conserved protein phosphatases reverses defects associated with mitochondrial DNA damage in Saccharomyces cerevisiae.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic inflammation during placental malaria (PM) caused by Plasmodium falciparum is most frequent in first-time mothers and is associated with poor maternal and fetal outcomes. In the first genome wide analysis of the local human response to sequestered malaria parasites, we identified genes associated with chronic PM, then localized the corresponding proteins and immune cell subsets in placental cryosections.
Publication Title
Genome-wide expression analysis of placental malaria reveals features of lymphoid neogenesis during chronic infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Treatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.
Publication Title
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In these microarray experiments, we characterize the gene expression of mammary epithelial cells (MCF10A cells) grown in either a traditional monolayer cell culture setting (2D) or on Matrigel, which induces single MCF10A cells to form organized acinar structures (3D). Morphogenesis of mammary epithelial cells into organized acinar structures in vitro is accompanied by widespread changes in gene expression patterns, including a substantial decrease in expression of Myc.
Publication Title
Epithelial cell organization suppresses Myc function by attenuating Myc expression.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the conversion of saturated fatty acids palmitate and stearate to monounsaturated fatty acids palmitoleate and oleate. During adipocyte differentiation, SCD expression increases concomitantly with several transcription factors and lipogenic genes.
Publication Title
Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples