Multiple comprehensive analyses identify that upregulation of Myomesin 2 suppresses cardiomyocyte proliferation

Mammalian cardiomyocytes lose their proliferative capacity shortly after birth; however, molecular mechanisms that regulate cardiomyocyte proliferation remain to be fully elucidated. This study aimed to identify genes that regulate cardiomyocyte proliferation through multiple comprehensive analyses. RNA-sequencing analysis was performed using proliferating neonatal rat cardiomyocytes. We also retrieved and analyzed publicly available single-cell RNA-sequencing datasets from rat hearts on postnatal days 1 and 7. Pseudotime trajectory analysis identified a cardiomyocyte cluster undergoing cell cycle exit at postnatal day 7. Comparative gene expression analysis of this cluster between postnatal day 1 and day 7 identified Myomesin 2 (Myom2) as a candidate for regulation of cardiomyocyte proliferation. Real time qRT-PCR analysis demonstrated that Myom2 expression increased during cardiac maturation. Further, we investigated the effect of Myom2 expression on cardiomyocyte proliferation. Immunofluorescence microscopic analysis revealed that adenoviral overexpression of Myom2 significantly reduced the proportion of proliferating cardiomyocytes and promoted cardiomyocyte binucleation. Collectively, these findings indicate that postnatal induction of Myom2 suppresses cardiomyocyte proliferation and promotes binucleation.