Authors: Yu Xia, Sierra Duca, Björn Perder, Friederike Dündar, Paul Zumbo, Miaoyan Qiu, Jun Yao, Yingxi Cao, Michael R. M. Harrison, Lior Zangi, Doron Betel, Jingli Cao
Published: 2022-12-13
DOI: 10.1038/s41467-022-35433-9
Source: Full article
AbstractThe epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked byptx3aandcol12a1bexpression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells andpdgfra+hapln1a+mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reducednrg1expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.