Abstract
Introduction: The cell cycle arrest of the mammalian adult cardiomyocytes is the main reason for limited cardiac regeneration. A complex network of intracellular molecules facilitates cell cycle progression, from which regulatory proteins are well studied. However, the non-protein compartments such as regulatory microRNAs (miRNAs) are underrepresented. Here, we explored the miRNAs with differential expression in proliferating and non-proliferating cardiomyocytes.
Methods: Candidate miRNAs with significant differential expression between 14-day and 45-day human embryonic stem cell-derived cardiomyocytes (hESC-CM) were identified using reanalysis of data set GSE35672. Human embryonic stem cells (hPSCs) were expanded and differentiated into cardiomyocytes by a cocktail of small molecules targeting Wnt/β-catenin and TGF-β signaling, and samples were collected for expression analysis of in silico-identified candidate miRNAs at days 10, 20, and 30 of differentiation.
Findings: miR-302d, miR-371-5p, and miR-372 were selected as candidate differentially expressed miRNAs (DEmiRNAs). While miR-302d and miR-371-5p expression did not repeat the in-silico results in cTNT+hESC-CM, miR-372 showed a significant downregulation from day 10 to day 30.
Conclusion: This finding suggests a possible regulatory effect of miRNA-372 in cell cycle arrest of mature cardiomyocytes.