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

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Item Type:Article
Title:In vivo single-cell RNA metabolic labeling resolves early transcriptional responders in the regenerating zebrafish heart
Creators Name:Mintcheva, Janita, Tseng, Tzu-Lun, Goumenaki, Pinelopi, Neuschulz, Anika, Senoussi, Anis, Lelek, Sara, Lim, Khai Lone, Ming, Zhitao, Schäfer, Ronny, Hnatiuk, Alisa, Ninov, Nikolay, Beisaw, Arica, McGrail, Maura, Ben Lai, Shih-Lei, Panáková, Daniela, Stainier, Didier Y. R. and Junker, Jan Philipp
Abstract: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 zebraf ish heart after injury. Within the first 6h, we detect activation of innate immune programs, including Toll-like receptor signaling, in a subset of macrophage-like immunecells.Analysisofa largersingle-cell dataset indicates that neutrophils also contribute to this early response. Guided by these data, weshowthat 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.
Keywords:Heart, Innate Immunity, Macrophages, Myeloid Differentiation Factor 88, Myocardium, Neutrophils, RNA, Regeneration, Signal Transduction, Single-Cell Analysis, Toll-Like Receptors, Zebrafish Proteins, Animals, Zebrafish
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:17
Number:1
Page Range:4073
Date:5 May 2026
Official Publication:https://doi.org/10.1038/s41467-026-72781-2
PubMed:View item in PubMed
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