ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes.

ABSTRACT: One of the earliest maturation steps in cardiomyocytes (CMs) is the sarcomere protein isoform switch between TNNI1 and TNNI3 (fetal and neonatal/adult troponin I). Here, we generate human induced pluripotent stem cells (hiPSCs) carrying a TNNI1^EmGFP and TNNI3^mCherry double reporter to monitor and isolate mature sub-populations during cardiac differentiation. Extensive drug screening identifies two compounds, an estrogen-related receptor gamma (ERRγ) agonist and an S-phase kinase-associated protein 2 inhibitor, that enhances cardiac maturation and a significant change to TNNI3 expression. Expression, morphological, functional, and molecular analyses indicate that hiPSC-CMs treated with the ERRγ agonist show a larger cell size, longer sarcomere length, the presence of t

SUBMITTER: Miki K 

PROVIDER: S-EPMC8217550 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature