The mammalian heart has a limited capacity to regenerate. Under certain conditions, however, cardiomyocyte proliferation has been observed, for example in resected neonatal hearts and in response to certain cytokine treatments. Nevertheless, the extent to which cardiomyocyte proliferation occurs both in steady state and after injury in the postnatal mouse is hotly debated, as studies are limited by a lack of reliable genetic tracing tools. Now, on p. 580, Zhongzhou Yang and colleagues use a p53-based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration through neonatal, adolescent and adult stages. The authors observed clonal expansion of p53+ cardiomyocytes in the neonatal heart, as well as in pre-adolescent and adult hearts. Interestingly, some of the labeled cardiomyocytes also formed larger clusters if given a longer tracing time, suggestive of a selectively long-lasting proliferative potential. The authors also investigated cardiomyocyte proliferation after cryo-injury and showed that p53+ cardiomyocytes exhibit cytomembrane localization of the sarcomeric protein cTnT during heart regeneration, consistent with previous studies. Finally, the authors demonstrated that the p53 genetic labeling system reliably traced proliferating cardiomyocytes following not only in cryo-injury, but also in two additional types of cardiac injury models in neonatal mice. This study reveals the specific lineage contribution to mammalian cardiac repair and provides evidence for the heterogeneity of cardiomyocytes in mammalian heart.
- © 2017. Published by The Company of Biologists Ltd