Transcriptomic analysis of ethanol, DMSO, I-CBP112 and C646 treatment on mouse embryonic fibroblasts (MEFs) during direct cardiac reprogramming

Direct cardiac reprogramming represents an attractive way of reversing heart damage caused by myocardial infarction. Yet, it is still in pre-clinical stage mainly due to the lack of efficacy with current transdifferentiation protocols. Here, we describe that dimethyl sulfoxide (DMSO) is capable of augmenting direct cardiac reprogramming in vitro. Treatment of Gata4, Hand2, Mef2c and Tbx5 (GHMT) - transduced mouse embryonic fibroblasts (MEFs) with 1% DMSO induced ~5 fold increase in the percentage of Myh6-mCherry+ cells, and significantly increased the global expression of cardiac genes. Transcriptomic studies were carried out to explore the underlying mechanism of how DMSO may enhance cardiac transdifferentiation. Overall design: RNA-seq was carried out on GHMT-transduced cells after 7 days of treatment with 0.1% ethanol, 1% DMSO, 5 uM I-CBP112 and 5 uM C646