Activation of ERRγ enhances mitochondrial and sarcomere maturation in human induced pluripotent stem cell-derived cardiomyocytes

We identified two cardiac maturation stimulators from 9,048 compounds using Troponin I1 (TNNI1) and Troponin I3 (TNNI3) double reporter hiPSC-derived CMs. An estrogen-related receptor gamma (ERRγ)-specific agonist increased the size of hiPSC-CMs and their mitochondrial content and enhanced their mitochondrial function. In addition, combination of this agonist with an inhibitor of S-phase kinase-associated protein 2 (SKP2) increased the TNNI3 expression more highly than previous methods and enhanced cardiac maturation-related gene expression profiles. mRNA profiles of hiPSC-CMs with conpounds were generated by deep sequencing, in triplicate, using Illumina Nextseq 500.