β-Catenin drives distinct transcriptional networks in proliferative and nonproliferative cardiomyocytes

Abstract

The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. By contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms for the developmental loss of cardiac regenerative capacity in mammals are not fully understood. Wnt/ β-catenin signalling has been proposed as a key cardioregenerative pathway driving cardiomyocyte proliferation. Here, we show that Wnt/β-catenin signalling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. By contrast, Wnt/ β-catenin signalling in adult mice is ca..