Revisiting Preadolescent Cardiomyocyte Proliferation in Mice.

Abstract

No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice Alkass et al Cell . 2015;163:1026–1036. Understanding cardiomyocyte cell cycle regulation after birth is key to optimizing regenerative strategies for the heart post injury, yet poses multiple technical challenges, as evidenced by recent studies that have arrived at divergent conclusions. In a recent publication in Cell , Alkass et al undertook multiple approaches to examine cardiomyocyte cell cycle regulation in the first 3 weeks after birth. Here, we summarize results of Alkass et al and 3 other groups in examining preadolescent cardiomyocyte cell cycle regulation, highlighting the distinct approaches and incumbent caveats . Understanding cardiomyocyte cell cycle activity during the perinatal and preadolescent period is extremely challenging and is a subject of intense debate. From a classical viewpoint, throughout embryonic development, cardiomyocytes progressively lose their ability to divide and proliferate. After the period between postnatal day 5 (P5) and 10 (P10), the second and final wave of nonreplicative DNA synthesis ends with binucleation of existing cardiomyocytes.1 Recently, Naqvi et al proposed that cardiomyocytes undergo an additional burst of synchronized proliferation on postnatal day 15 (P15) that results in a 40% increase in the number of cardiomyocytes.2 However, in a recent study, Alkass et al observed that an increase in cardiomyocyte number after birth is largely restricted to the first postnatal week, with no significant increase in number after postnatal day 11.3 Consistent with Alkass et al, 2 other groups were not able to substantiate a proliferative burst of cardiomyocytes during preadolescence between the second and third postnatal weeks.4,5 Interestingly, Alkass et al observed a peak of polyploidization of binucleated cardiomyocytes between the second and third postnatal weeks, introducing further complexity to the model of cardiomyocyte cell …