Analysis of microRNA transcriptomic changes in ethanol-exposed human embryonic stem cell (hESC)-derived cortical interneurons using small RNA sequencing. Analysis of microRNA transcriptomic changes in ethanol-exposed human embryonic stem cell (hESC)-derived cortical interneurons using small RNA sequencing

Purpose: The goal of this study to use ethanol-exposed human embryonic stem cell (hESC)-derived neural cells as models to investigate microRNA expression changes in the brains of subjects with alcohol use disorder (AUD). Methods: hESCs were differentiated into neural cells (mainly cortical interneurons), which were then cultured in media with or without ethanol (50-100 mM) for 7 days (by duplicate experiments). Total RNAs were extracted from hESC-derived neural cells (with or without ethanol exposure) for small RNA sequencing. The sequence reads were processed using the Comprehensive Analysis Pipeline for miRNA Sequencing Data (CAP-miRseq) workflow. Ethanol-induced miRNA transcriptomic changes were analyzed by the Limma-Voom method. Results: A 7-day ethanol exposure led to differential expression of six miRNAs (absolute FC>2.0 & P2-fold increase & P 2-fold decrease & P < 0.05) due to ethanol exposure. Conclusions: The hESC-derived neural cell model study can partially validate miRNA transcriptomic changes in postmortem brains of subjects with alcohol use disorder. Overall design: hESC-derived neural cells exposed (or unexposed) to ethanol for 7 days