The Role of Isocitrate Dehydrogenases in Direct Reprogramming to Cardiomyocytes.

Abstract

© RADCLIFFE CARDIOLOGY 2021 Access at: www.ECRjournal.com Objectives: Direct reprogramming with introduction of Gata4, Mef2c and Tbx5 (GMT) genes involved in cardiogenesis can convert fibroblasts to induced cardiomyocyte-like cells (iCMs), whereas only a low percentage of iCMs are obtained due to the low proliferative capacity. Recent studies suggest that oestrogen-related receptors (ERRs) are involved in cardiomyocyte maturation during the differentiation from pluripotent stem cells. In addition, ERRγ regulates the density and morphology of mitochondria in matured cardiomyocytes accounting for prominent aerobic metabolism. ERRγ is also known to induce the transcription of isocitrate dehydrogenases (IDHs), one of the tricarboxylic acid cycle regulators. In the present study, we investigate whether ERRγ-IDHmediated mitochondria regulation is involved in cellular metabolism during direct reprogramming to iCMs.