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Origin and function of activated fibroblast states during zebrafish heart regeneration

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Item Type:Article
Title:Origin and function of activated fibroblast states during zebrafish heart regeneration
Creators Name:Hu, B. and Lelek, S. and Spanjaard, B. and El-Sammak, H. and Simões, M.G. and Mintcheva, J. and Aliee, H. and Schäfer, R. and Meyer, A.M. and Theis, F. and Stainier, D.Y.R. and Panáková, D. and Junker, J.P.
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.
Keywords:Animals, Zebrafish
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group
Date:21 July 2022
Official Publication:https://doi.org/10.1038/s41588-022-01129-5
PubMed:View item in PubMed

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