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bioRxiv · 10.1101/2022.10.26.513031

Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration

Xia, Y.·Duca, S.·Perder, B.·Dundar, F.·Zumbo, P.·Qiu, M.·Yao, J.·Cao, Y.·Harrison, M. R.·zangi, l.·Betel, D.·Cao, J.
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Abstract

The 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 defined the epithelial and mesenchymal subsets of the epicardium. We further identified a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by ptx3a and col12a1b expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and pdgfra+hapln1a+ mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgf{beta} pathway. Conditional ablation of aEPCs blocked heart regeneration through reduced Nrg1 expression 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.

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Xia, Y., Duca, S., Perder, B., Dundar, F., Zumbo, P., Qiu, M., Yao, J., Cao, Y., Harrison, M. R., zangi, l., Betel, D., Cao, J.. 2022-10-28. Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration. https://doi.org/10.1101/2022.10.26.513031

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