Dataset Information

Global gene expression profiles of cardiomyocytes differentiated from human pluripotent stem cells (hiPSC-CMs) in 3D culture exposed to ethanol

ABSTRACT: Methods: RNA-seq libraries were prepared using the Illumina TruSeq RNA kit and the TrueSeq method was employed for mRNA enrichment. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq2500 system. Reads were mapped on the Human Genome Reference and normalized expression table was generated. Results: RNA-seq results reveal gene expression of cardiac toxicity in hiPSC-CMs that are consistent with alcohol-induced pathophysiology observed in animal models. For example MMP9 is among the top 5 upregulated genes in ethanol-treated hiPSC-CMs, MMP9 concentrations are significantly higher in human sera of chronic alcohol abusers and MMP9 mRNA and protein levels are increased in the myocardium of rats following acute ethanol exposure. Conclusions: Data demonstrate significant alteration in gene expression, among the top 60 genes significantly altered by ethanol exposure, 8 genes are involved in ion channels, which may be in part contributing to the abnormal intracellular Ca2+ transients. Ethanol up-regulated the expression of genes associated with collagen metabolism and extracellular matrix (MMP9, EMID1, COL14A1), most of the downregulated genes are involved in cardiovascular system development (NPPB, DNAAF3), actin filament-based process (LMOD2, MYH4) and muscle contraction (MYL2). These findings are consistent with previous studies showing a correlation between alcohol exposure and defects in heart and circulatory system development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125917 | GEO | 2019/01/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:ABSTRACT Background: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: Human iPSC-CMs were infected with a luciferase-expressing mutant of the coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs. Viral proliferation on hiPSC-CMs was subsequently quantified using bioluminescence imaging. For drug screening, select antiviral compounds including interferon beta 1 (IFNβ1), ribavirin, pyrrolidine dithiocarbamate (PDTC), and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of some of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with the reported drug effects in previous studies. Finally, mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways within these hiPSC-CMs after IFNβ1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to confirm antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that could be used to screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion. For this experiment, human induced pluripotent stem cell derived cardiomyocytes were infected with coxsackievirus at multiplicity of infection (MOI) of 5 for 8 hours. Cells were treated with and without interferon beta 1 in order to determine if treatment activates antiviral response genes and/or viral clearance pathways. 4 total samples (2 for each condition) were analyzed

Dataset Information

Global gene expression profiles of cardiomyocytes differentiated from human pluripotent stem cells (hiPSC-CMs) in 3D culture exposed to ethanol

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets