Comparative Gene Expression Analyses Reveal Distinct Molecular Signatures between Differentially Reprogrammed Cardiomyocytes

• Main Authors: Yang Zhou, Li Wang, Ziqing Liu, Sahar Alimohamadi, Chaoying Yin, Jiandong Liu, Li Qian
• Format: Article
• Language: English
• Published: Elsevier 2017-09-01
• Series: Cell Reports
• Subjects: cardiac reprogramming; cardiomyocyte; iCM; iPSC; cardiac differentiation; gene expression profiling
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717312664

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-CMs and iCMs 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, whereas iCMs exhibit a maturation status that more closely resembles that of adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis, whereas 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.