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Mintcheva, J.* ; Tseng, T.L.* ; Goumenaki, P.* ; Neuschulz, A.* ; Senoussi, A.* ; Lelek, S.* ; Lim, K.L.* ; Ming, Z.* ; Schäfer, R.* ; Hnatiuk, A. ; Ninov, N. ; Beisaw, A.* ; McGrail, M.* ; Lai, S.B.* ; Panáková, D.* ; Stainier, D.Y.R.* ; Junker, J.P.*

In vivo single-cell RNA metabolic labeling resolves early transcriptional responders in the regenerating zebrafish heart.

Nat. Commun. 17:4073 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The adult zebrafish heart can regenerate after injury, but the earliest gene expression changes that trigger this process remain poorly understood. Here we show that in vivo single-cell RNA metabolic labeling, which marks newly made RNA in individual cells, can capture rapid responses in the adult zebrafish heart after injury. Within the first 6 h, we detect activation of innate immune programs, including Toll-like receptor signaling, in a subset of macrophage-like immune cells. Analysis of a larger single-cell dataset indicates that neutrophils also contribute to this early response. Guided by these data, we show that macrophage-specific inhibition of the Toll-like receptor adaptor MyD88 reduces the pro-inflammatory macrophage response at the injury site and improves early hallmarks of regeneration. Our work establishes RNA metabolic labeling as a useful approach for measuring acute responses in vivo at single-cell resolution and identifies early immune-cell activation as a tunable component of heart regeneration.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cryoinjury; Defines; Genes
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 17, Issue: 1, Pages: , Article Number: 4073 Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
Grants U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)
Deutsche Forschungsgemeinschaft (German Research Foundation)
Studienstiftung des Deutschen Volkes (German National Academic Foundation)
European Molecular Biology Organization (EMBO)
TAIWAN (NSTC) - LITHUANIA (LMT) joint research grant (NSTC 113-2923-B-001-003-MY2)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (200
Helmholtz Association
Deutsches Zentrum fr Herz-Kreislaufforschung (Deutsches Zentrum fr Herz-Kreislaufforschung e.V.)
Fondation Leducq