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GSE7123
Homo sapiens
199 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Time series of gene expression arrays before and during treatment of Hepatitis C; days 0, 1, 2, 7, 14 and 28 for 69 participants (IDs 1 through 69 are used).
Publication Title
Changes in gene expression during pegylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We sought to obtain gene signature specific of high oxidative phsophorylation function.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
It has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
It has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
Illumina HiSeq 2000
Description
We performed whole-genome stability measurements for MDA-MB-231 and its highly metastatic derivative MDA-LM2. Our goal was to identify post-transcriptonal regulons that are deregulated en route to higher metastatic capacity. Overall design: Cells were pulsed with 4-thiouridine for 2 hours and then RNA was extracted at 0, 2, 4, and 7 hr time-points in quadruplicate from each cell line. 4sU labeling followed by RNA-seq was then used to measure the abundance of transcripts in each population. A decay rate was estimated based on the rate at which transcript abundance was reduced at these time-points.
Publication Title
Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Homo sapiens, Rattus norvegicus
- 24 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified signature miRNAs in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated.
Publication Title
MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Ppargc1a overexpression in heart tissue measured using RNA sequencing Overall design: RNA expression profiles were generated using RNA-seq from control (N=3) and Ppargc1a overexpressing (N=3) mice
Publication Title
Peroxisome proliferator-activated receptor-γ coactivator 1 α1 induces a cardiac excitation-contraction coupling phenotype without metabolic remodelling.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We show that Bmx-deficiency reduces angiotensin II -induced cardiac hypertrophy and pathological gene expression
Publication Title
Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
The cellular and molecular aspects of post-infarct left-ventricle remodeling in presence of type-2 diabetes is poorly understood. In this study we have addressed the cellular and molecular aspects underlying post-infarct left-ventricle remodeling in type 2 diabetic (T2DM) mice using genome-wide mRNA-sequencing. Myocardial infarction was induced by ligating left-anterior descending artery (LAD) in 12-14 month old T2DM and control mice. Cardiac MRI was performed at baseline, day 7 and 14 post-LAD ligation. Blood and tissue samples were collected for biochemical and immunohistochemical, molecular biology analysis after sacrification at day 7 and 14. Genome-wide mRNA sequencing analysis was performed from left-ventricular tissues collected at day 7 post-LAD ligation. Mitochondrial dynamics, Leukocyte recruitment and Collagen I deposition were analyzed using electron microscopy, fluorescent assisted cell sorting (FACS) and fourier-transform infra-red (FTIR) spectroscopy from left ventricular tissues collected at day 7 and 14 post-LAD ligation. Cardiac ejection fraction (EF) and stroke volume (SV) were significantly reduced along with increased mortality in T2DM compared to controls. Ingenuity pathway analyses of differentially expressed genes were enriched for mitochondrial dysfunction, TCA cycle and fatty acid oxidation. Additionally, upstream transcription factor analysis showed inhibition of PGC1a, PGC1b, ESRRA, ESRRB and TFAM in infarcted myocardium of T2DM mice. Electron microscopy analysis showed an altered mitochondrial dynamics and cardiomyocyte death in ischemic myocardium of T2DM mice. Leukocytes exhibited an altered phenotype in ischemic myocardium of T2DM mice. Neovascularization was impaired and collagen deposition was increased in ischemic myocardium of T2DM mice. We conclude that an altered mitochondrial dynamics, cell death modalities, leukocyte phenotype, neovascularization responses and fibrosis may contribute to an increased mortality after myocardial infarction in T2DM. Modulation of mitochondrial dynamics and cardiomyocyte cell death modalities may offer a novel therapeutic target. Overall design: Myocardial infarction was induced by ligating left anterior descending artery (LAD). Total RNA was isolated from remote, Infarct and border zones at day 7 after myocardial infarction. Poly (A)+RNA fraction was subjected to RNA sequencing using Illumina HiSeq.
Publication Title
Aggravated Postinfarct Heart Failure in Type 2 Diabetes Is Associated with Impaired Mitophagy and Exaggerated Inflammasome Activation.
Sample Metadata Fields
No sample metadata fields
View Samples