GSE125917
Global gene expression profiles of cardiomyocytes differentiated from human pluripotent stem cells (hiPSC-CMs) in 3D culture exposed to ethanol
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. Overall design: RNA-sequencing analysis was performed to compare global gene expression profiles of cardiomyocytes under ethanol treatment vs. control.