PUBLICATION
Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration
- Authors
- Xia, Y., Duca, S., Perder, B., Dündar, F., Zumbo, P., Qiu, M., Yao, J., Cao, Y., Harrison, M.R.M., Zangi, L., Betel, D., Cao, J.
- ID
- ZDB-PUB-221216-7
- Date
- 2022
- Source
- Nature communications 13: 77047704 (Journal)
- Registered Authors
- Cao, Jingli, Harrison, Michael
- Keywords
- none
- Datasets
- GEO:GSE202836
- MeSH Terms
-
- Animals
- Epithelial-Mesenchymal Transition/genetics
- Extracellular Matrix Proteins/metabolism
- Heart/physiology
- Heart Injuries*/genetics
- Pericardium
- Proteoglycans/metabolism
- Stem Cells/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36513650 Full text @ Nat. Commun.
Citation
Xia, Y., Duca, S., Perder, B., Dündar, F., Zumbo, P., Qiu, M., Yao, J., Cao, Y., Harrison, M.R.M., Zangi, L., Betel, D., Cao, J. (2022) Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration. Nature communications. 13:77047704.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping