Postnatal expression of cell cycle promoter Fam64a causes heart dysfunction by inhibiting cardiomyocyte differentiation through repression of Klf15.

ABSTRACT: Introduction of fetal cell cycle genes into damaged adult hearts has emerged as a promising strategy for stimulating proliferation and regeneration of postmitotic adult cardiomyocytes. We have recently identified Fam64a as a fetal-specific cell cycle promoter in cardiomyocytes. Here, we analyzed transgenic mice maintaining cardiomyocyte-specific postnatal expression of Fam64a when endogenous expression was abolished. Despite an enhancement of cardiomyocyte proliferation, these mice showed impaired cardiomyocyte differentiation during postnatal development, resulting in cardiac dysfunction in later life. Mechanistically, Fam64a inhibited cardiomyocyte differentiation by repressing Klf15, leading to the accumulation of undifferentiated cardiomyocytes. In contrast, introduction of Fam64a in d

SUBMITTER: Hashimoto K 

PROVIDER: S-EPMC9118685 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature