PUBLICATION
Origin and function of activated fibroblast states during zebrafish heart regeneration
- Authors
- Hu, B., Lelek, S., Spanjaard, B., El-Sammak, H., Simões, M.G., Mintcheva, J., Aliee, H., Schäfer, R., Meyer, A.M., Theis, F., Stainier, D.Y.R., Panáková, D., Junker, J.P.
- ID
- ZDB-PUB-220723-3
- Date
- 2022
- Source
- Nature Genetics 54(8): 1227-1237 (Journal)
- Registered Authors
- Meyer, Alexander, Panáková, Daniela, Stainier, Didier
- Keywords
- none
- Datasets
- GEO:GSE159032, GEO:GSE158919
- MeSH Terms
-
- Animals
- Cell Proliferation
- Fibroblasts
- Heart/physiology
- Myocytes, Cardiac/physiology
- Regeneration/genetics
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- PubMed
- 35864193 Full text @ Nat. Genet.
Citation
Hu, B., Lelek, S., Spanjaard, B., El-Sammak, H., Simões, M.G., Mintcheva, J., Aliee, H., Schäfer, R., Meyer, A.M., Theis, F., Stainier, D.Y.R., Panáková, D., Junker, J.P. (2022) Origin and function of activated fibroblast states during zebrafish heart regeneration. Nature Genetics. 54(8):1227-1237.
Abstract
The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping