Comparative gene expression analyses reveal distinct molecular signature between differentially reprogrammed cardiomyocytes

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes, iCMs) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CM and iCM are still unknown. Here we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status while iCMs exhibit maturation status that more resemble adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis while iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches. To dissect the similarities and differences of gene expression profiles between reprogrammed cardiomyocytes (CMs), we generated contractile CMs by iPSC differentiation and direct reprogramming from neonatal cardiac fibroblasts (neoCFs) of the same origin. We collected two independent iPSC line-derived beating CMs and iCMs in duplicate for microarray analysis and also included duplicate of primary neoCFs and neoCMs isolated from transgenic pups as controls. Additionally, we harvested reprogrammed cells at different time points (D0, D3, D5, D7, D10 and D14) during early iCM reprogramming. Microarray was performed on Agilent mouse 8x60K GE 1color platform.