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Primary human hepatocyte transcriptomic statin response

ABSTRACT: Primary human hepatocyte transcriptomic statin response

PROVIDER: PRJNA789648 | ENA |

REPOSITORIES: ENA

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Primary human hepatocyte transcriptomic statin response

Project description:We have previously identified a number of statin-responsive genes in human cell lines, but in some cases, these findings may not be relevant in vivo. Here, we statin exposed primary human hepatocytes from four different donors to identify statin-responsive genes in this biologically relevant cell type. We also compared the effects of statin on gene expression between these primary cells and our previous datasets in other cell lines to identify overlapping effects of interest.

2024-12-16 | GSE191092 | GEO

Transcriptome (RNA-seq) of statin-treated human primary myotubes

Project description:Statin-induced myopathy is a common side-effect but its mechanisms in human skeletal muscle have never been explained satisfyingly. We exposed 25 different primary human muscle cell lines to either a lipophilic or a hydrophilic statin, quantified cholesterol, mevalonate, proliferation, differentiation, and performed a comprehensive transcriptome and proteome analysis. We found reduced mevalonic acid (MVA) and cholesterol levels demonstrating incorporation of statins into the cells. Statins also significantly impaired proliferation and differentiation. Using an integrated pathway analysis approach with transcriptome and proteome data from statin-treated human primary myotubes, we modelled a novel statin-induced metabolism network for human muscle cells. This analysis confirmed the effect of statins on cholesterol biosynthesis but also uncovered alterations of acetyl CoA-dependent lipid and fatty acid metabolism

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Primary hepatocyte transcriptional response to Pink1 over-expression by adenovirus

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A comprehensive transcriptomic comparison of hepatocyte model systems

Project description:We generated intrahepatic cholangiocyte organoids and fetal hepatocyte organoids to compare their transcriptomic profile with liver tissue, primary human hepatocytes, and other hepatocyte model systems.

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CD100 stimulation on primary hepatocyte

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Liver transcriptome of statin-treated patients

Project description:Background: Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. Methods: An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Results: We determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. Patients on statin treatment showed higher diabetes prevalence (OR=2.67; 95%CI, 1.60-4.45; P= 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein-1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism. Conclusions: DNL gene activation profile in response to statins was associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.

2019-05-15 | GSE130991 | GEO

Transcriptome (RNA-seq) of statin-treated human primary myotubes

Project description:Transcriptome (RNA-seq) of statin-treated human primary myotubes

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CD100 stimulation on primary hepatocyte

Project description:To determine the effects of CD100 stimulation on hepatocyte, we have employed mRNA microarray expression profiling as a discovery platform to identify genes with the potential to response to CD100 stimulation, for evaluating the CD100 effects on the metabolism of hepatocyte. The primary hepatocyte, but not the hepatocellular cell lines, was used for the CD100 stimulation experiment ex vivo, and different expressing genes was identified that distinguished among MOCK, CD100 stimulated and TNF-a-stimulated (as a positive control) groups.

2024-05-21 | GSE252134 | GEO

Genome-wide association study of therapeutic response to statin drugs in cardiovascular disease

Project description:GWAS of Statin response

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