Binucleation of cardiomyocytes: the transition from a proliferative to a terminally differentiated state

Abstract

Cardiomyocytes possess a unique ability to transition from mononucleate to the mature binucleate phenotype in late fetal development and around birth. Mononucleate cells are proliferative, whereas binucleate cells exit the cell cycle and no longer proliferate. This crucial period of terminal differentiation dictates cardiomyocyte endowment for life. Adverse early life events can influence development of the heart, affecting cardiomyocyte number and contributing to heart disease late in life. Although much is still unknown about the mechanisms underlying the binucleation process, many studies are focused on molecules involved in cell cycle regulation and cytokinesis as well as epigenetic modifications that can occur during this transition. Better understanding of these mechanisms could provide a basis for recovering the proliferative capacity of cardiomyocytes.