Poster #076
Nucleoside balance drives cardiomyocyte proliferation by E2F1-TFDP1 axis
Mentor: Yin Wang, Post-Doc
Cardiac diseases are often exacerbated by the heart’s limited ability to regenerate, largely due to the poor proliferative capacity of adult cardiomyocytes. Since excess individual nucleosides are known to impair proliferation during S phase in cancer cells, we treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with varying concentrations of nucleosides, both individually and in combination. We identified certain balanced combinations that enhanced iPSC-CM proliferation in vitro. Interestingly, nucleosides enhanced the heart function of mice suffering from MI and promoted cardiomyocyte proliferation in border zones in vivo. An analysis of Multiomic-seq integrated with H3K27ac-ChIP-seq showed that TFDP1 may play a key role in nucleoside balance. Knock-down and overexpression results showed that nucleosides phosphorylated RB1 protein, releasing E2F1 transcription factors, and the latter promoted TFDP1 expression, which enhanced the Cyclin E1-CDK2 complex activity for cell cycles. Our findings highlight nucleoside balance as an essential regulator of cardiomyocyte proliferation.