 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 22, 2022 |
| Title |
An injury-associated transient progenitor state in the epicardium mediates heart regeneration |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Adult zebrafish regenerate heart muscle after severe cardiac damage without significant scarring. The epicardium, a mesothelial cell sheet covering the vetebrate heart, is activated by injury and supports muscle regeneration through paracrine effects and as a source of multipotent cells. The understudied cellular heterogeneity of the adult epicardium during heart regeneration has constrained the effort in mobilizing the epicardium for heart repair. To dissect epicardial cell states and the underlying mechanisms that lead to successful heart regeneration in zebrafish, we performed single-cell RNA-sequencing of isolated epicardial cells from the regenerating adult heart and revealed their dynamic cellular heterogeneity. We defined the epithelial and mesenchymal layers of the epicardium and identified a transiently activated epicardial progenitor cell (aEPC) subpopulation that expresses aldh1a2, ptx3a, col12a1b and marcksb. Upon heart amputation injury, aEPCs emerge from the existing epicardial cells, migrate to enclose the wound, and disappear as regeneration progresses. Genetic lineage tracing combined with modified RNA labelling confirmed an epithelial-mesenchymal transition (EMT) process of aEPCs and their differentiations to pdgfrb+ mural cells and pdgfra+hapln1a+ mesenchymal fibroblast-like cells that support heart regeneration. Genetic ablation of aEPCs blocked wound closure of the injured ventricle, suppressed cardiomyocyte proliferation, and disrupted heart regeneration. Our findings define a transient progenitor state of the adult epicardium that is an indispensable driver of zebrafish heart regeneration and identified ptx3a as a regeneration-specific non-ontogenetic regulator of the epicardium.
|
| |
|
| Overall design |
Single-cell RNA sequencing of isolated epicardial cells from uninjured zebrafish hearts and hearts after amputation injury
|
| |
|
| Contributor(s) |
Xia Y, Duca S, Perder B, Dündar F, Zumbo P, Qiu M, Cao Y, Harrison MR, Zangi L, Betel D, Cao J |
| Citation(s) |
36513650 |
| Submission date |
May 12, 2022 |
| Last update date |
Jan 06, 2023 |
| Contact name |
Friederike Dündar |
| E-mail(s) |
frd2007@med.cornell.edu
|
| Organization name |
Weill Cornell Medicine
|
| Department |
Physiology & Biophysics
|
| Lab |
Applied Bioinformatics Core
|
| Street address |
1300 York Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21741 |
Illumina HiSeq 4000 (Danio rerio) |
|
| Samples (3) |
| GSM6133971 |
3-days post amputation, epicardial cells, scRNA-seq |
| GSM6133972 |
7-days post amputation, epicardial cells, scRNA-seq |
| GSM6133973 |
epicardial cells, scRNA-seq |
|
| Relations |
| BioProject |
PRJNA837476 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE202836_RAW.tar |
91.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
