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GSE52308
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Publication Title
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: CHOP_1.0_ENTREZG (huex10st)
Description
Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.
Publication Title
Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 104 Downloadable Samples
Illumina HiSeq 2000
Description
Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction. Overall design: Endothelium from hypertensive mice were acutely extracted at two different ages (4 weeks and 22 weeks) and compared to endothelium from 22 week old normotensive mice.
Publication Title
Endothelial transcriptomics reveals activation of fibrosis-related pathways in hypertension.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adenovirus infection leads to increased glycolytic metabolism in host cells. Expression of a single gene product encoded within the E4 early transcription region, E4ORF1, is sufficient to promote increased glycolytic flux in cultured epithelial cells.
Publication Title
Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
KSHV promotes endothelia to mesenchymal transformation (EntMT) in EAHY cells
Publication Title
Kaposi sarcoma herpesvirus promotes endothelial-to-mesenchymal transition through Notch-dependent signaling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this analysis was to investigate the targets of the influenza A host shutoff ribonuclease PA-X. We profiled the relative levels of cellular RNAs in cells infected with influenza A virus (A/PuertoRico/8/1934 H1N1) comparing wild-type and mutants that make reduced levels of PA-X and/or make a truncated and inactive PA-X. We also profiled relative RNA levels in cells overexpressing wild-type PA-X or a catalytically inactive mutant (D108A). Overall design: for extopic expression, PA-X (from the A/PuertoRico/8/1934 H1N1 (PR8) strain) was expressed in A549 cells using a doxycyline-inducible transgene for 18 hrs; for infection, A549 cells were infected with the wild-type PR8 strain or mutant strain that carried mutations that reduce PA-X production or activity for 15 hrs. rRNA deplete RNA was subjected to high-throughput sequencing
Publication Title
The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively.
Publication Title
Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 198 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported.
Publication Title
Earliest changes in the left ventricular transcriptome postmyocardial infarction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant “persister” cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets. Overall design: 3 biological replicates of BT474 persister cells, two biological replicates of BT474 parental cells
Publication Title
Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used Kras/Hras/Nras-triple knockout MEFs expressing recombinant Nras to test the off-target effect of 2 Kras siRNAs at different transfection concentrations.
Publication Title
Development of siRNA payloads to target KRAS-mutant cancer.
Sample Metadata Fields
Specimen part
View Samples