Heterogeneous pdgfrβ+ cells regulate coronary vessel development and revascularization during heart regeneration.

Overview

Endothelial cells emerge from the atrioventricular canal (AVC) to form coronary blood vessels in juvenile zebrafish hearts. We find that pdgfrβ is first expressed in the epicardium around the AVC and later becomes localized mainly in the mural cells. Pdgfrβ mutant fish show severe defects in mural cell recruitment and coronary vessel development. Single cell RNA sequencing analyses identified Pdgfrβ+ cells as epicardium derived cells (EPDCs) and mural cells. Mural cells associated with coronary arteries also express cxcl12b and smooth muscle cell markers. Interestingly, these mural cells remain associated with coronary arteries even in the absence of Pdgfrβ, although smooth muscle gene expression is downregulated. We find that pdgfrβ expression dynamically changes in EPDCs of a regenerating heart. Differential gene expression analyses of pdgfrβ+ EPDCs and mural cells suggest that they express genes important for regeneration after heart injuries. mdka was identified as a highly upregulated gene in pdgfrβ+ cells during heart regeneration. However, pdgfrβ but not mdka mutants show defects in heart regeneration after amputation. Our results demonstrate that heterogeneous pdgfrβ+ cells are essential for coronary development and heart regeneration.