Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140981 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Statins are widely used cholesterol-lowering drugs that inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis. In some cases, however, these drugs may cause a number of toxic side effects in hepatocytes and skeletal muscle tissue. Currently, the specific molecular mechanisms that cause these adverse effects are not sufficiently understood. In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at five time points upon atorvastatin treatment. A novel systems-level analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor binding specificities, protein-protein interactions and protein-drug interactions. Several previously unknown transcription factors, regulatory cofactors and signaling molecules were found to be involved in atorvastatin-responsive gene expression. Some novel relationships, e.g., the regulatory influence of nuclear receptor NR2C2 on CYP3A4, were successfully validated in wet-lab experiments. Whole-genome Affymetrix U133 Plus 2.0 (Affymetrix, Santa Clara, CA) microarray measurements were conducted using samples of primary human hepatocytes cultured from six individuals (i.e., hh62, hh65, hh67, hh79, hh80 and hh81). Each sample was treated with atorvastatin and dimethylsulfoxide (DMSO), which was used as a control substance. Microarray measurements were performed at five time points (6 h, 12 h, 24 h, 48 h and 72 h) after the drug stimulus.
2011-08-31 | E-GEOD-29868 | biostudies-arrayexpress
Project description:Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming
| PRJNA234510 | ENA
Project description:A map of the PPARα transcription regulatory network for primary human hepatocytes
| PRJNA231926 | ENA
Project description:Acetaminophen-induced gene expression profiles in sandwich-cultured primary human hepatocytes
| PRJNA110013 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Predicting response to drug or xenobiotic exposure is vital to risk assessment and clinical response rates. Primary human hepatocytes are commonly used to evaluate liver drug metabolism and toxicity. They are the most physiologically relevant in vitro model, retaining expression of most ADME-relevant genes. However, human hepatocytes are source limited, have high donor variability, only survive short term in culture, and lack selection for specific genetic profiles. To overcome the limitations associated with primary hepatocytes we and others are investigating the potential of pluripotent stem cells as an alternative or complementary source for generating hepatocytes. Pluripotent stem cells offer advantages over primary hepatocytes because stem cells have high replicative capacity, potentially providing a limitless source of hepatocytes. Stem cell derived hepatocytes (SCDHs) may also provide an improved in vitro system for evaluating pharmacogenetic relationships, e.g. cytochrome P450 (CYP) enzymes and their impact on drug metabolism and toxicity. To demonstrate the utility of SCDHs in pharmacogenetic screening, we genotyped the five commonly used WiCell® human embryonic stem cell lines (hESC), H1, H7, H9, H13 and H14.
2016-05-24 | GSE53889 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Trovafloxacin-Induced Gene Expression Changes: Comparison of Primary Human Hepatocytes to HepG2 Cells
| PRJNA102723 | ENA
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO