Endothelial Cells Contribute to Generation of Adult Ventricular Myocytes during Cardiac Homeostasis

Cardiac tissue undergoes renewal with low rates. Although resident stem cell populations have been identified to support cardiomyocyte turnover, the source of the cardiac stem cells and their niche remain elusive. Using Cre/Lox-based cell lineage tracing strategies, we discovered that labeling of endothelial cells in the adult heart yields progeny that have cardiac stem cell characteristics and express Gata4 and Sca1. Endothelial-derived cardiac progenitor cells were localized in the arterial coronary walls with quiescent and proliferative cells in the media and adventitia layers, respectively. Within the myocardium, we identified labeled cardiomyocytes organized in clusters of single-cell origin. Pulse-chase experiments showed that generation of individual clusters was rapid but confined to specific regions of the heart, primarily in the right anterior and left posterior ventricular walls and the junctions between the two ventricles. Our data demonstrate that endothelial cells are an intrinsic component of the cardiac renewal process. [Display omitted] •Endothelial cells have cardiogenic potential in the adult heart•The endothelial-based cardiogenic process is rapid but spatially restricted•Endothelial cells produce quiescent and proliferative cardiac stem cells•Coronary arteries serve as radially organized cardiac stem cell niches The heart regenerates cardiomyocytes at low rates throughout life. Using Cre/Lox technology, Fioret et al. generated a fate map of vascular cells in healthy adult hearts and found that endothelial cells have cardiogenic potential, contributing to cardiac regeneration. The renewal process is rapid but restricted to specific areas of the myocardium. The regenerative niche is localized within the coronary arteries and generates quiescent and proliferative progeny expressing cardiac stem cell markers and early-stage cardiac differentiation genes.