Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration.

Autor: Xia Y; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Duca S; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Perder B; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Dündar F; Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Applied Bioinformatics Core, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Zumbo P; Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Applied Bioinformatics Core, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Qiu M; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Yao J; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Cao Y; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Harrison MRM; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Zangi L; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Betel D; Applied Bioinformatics Core, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.; Institute for Computational Biomedicine, Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Cao J; Cardiovascular Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA. jic4001@med.cornell.edu.; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA. jic4001@med.cornell.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 13; Vol. 13 (1), pp. 7704. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1038/s41467-022-35433-9
Abstrakt: 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 define the epithelial and mesenchymal subsets of the epicardium. We further identify 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 Tgfβ pathway. Conditional ablation of aEPCs blocks 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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