Identification of a multipotent Twist2-expressing cell population in the adult heart

Significance Adult mammalian hearts have limited self-renewal capacity. Although mounting evidence indicates that new cardiomyocytes are derived from dedifferentiation and proliferation of existing cardiomyocytes, the contribution of adult cardiac progenitors to cardiomyocyte renewal during homeostasis and upon injury remains under debate. The basic helix–loop–helix transcription factor Twist2 is expressed in interstitial cells in the adult myocardium. Using genetic lineage tracing, we identified a Twist2-expressing cell population that gives rise to a small number of adult cardiomyocytes in vivo. These Twist2-expressing cells can differentiate into cardiomyocytes, endothelial cells, and fibroblasts in culture and contribute to cardiac renewal through cell fusion and de novo differentiation. Our findings add Twist2-expressing cells to the cellular constituents involved in adult cardiac maintenance and remodeling.