Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice

Abstract

Pluripotency factor drives cardiogenesis Research indicates that the adult mammalian heart does not contain cardiac stem cells and the vast majority of cardiomyocytes do not divide. Heart regeneration is thus limited after injury. The postmitotic nature of cardiomyocytes blocks cardiac tumor formation but at the same time minimizes cardiomyocyte renewal. Chen et al . report that cell type–specific expression of pluripotency factors dedifferentiates adult cardiomyocytes to a state that resembles fetal cardiomyocytes, enabling adult cardiomyocytes to reenter mitosis (see the Perspective by Wang and Blau). Cardiomyocytes can be reprogrammed to a pluripotent state when expression of pluripotency factors is sustained over an extended period. If cardiomyocytes are only partially reprogrammed, the heart regenerates without tumor formation. —BAP