Spatiotemporal dynamics of the cardioimmune niche during lesion repair

Chan ASF, Greiner J, Marschhäuser L, Brennan TA, Perez-Feliz S, Agrawal A, Hemmer H, Sinning K, Cheung JWL, Iqbal Z, Klesen A, Vico TA, Aprea J, Hilgendorf I, Seidel T, Vaeth M, Rog-Zielinska EA, Kohl P, Schneider-Warme F, Grün D (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nature Cardiovascular Research Springer Nature

Book Volume: 4

Pages Range: 1550-1572

Journal Issue: 11

DOI: 10.1038/s44161-025-00739-6

Abstract

The heart is one of the least regenerative organs in humans, and ischemic heart disease is the leading cause of death worldwide. Understanding the cellular and molecular processes that occur during cardiac wound healing is an essential prerequisite to reducing health burden and improving cardiac function after myocardial tissue damage. Here, by integrating single-cell RNA sequencing with high-resolution spatial transcriptomics, we reconstruct the spatiotemporal dynamics of the fibrotic niches after cardiac injury in adult mice. We reveal a complex multicellular network that regulates cardiac repair, including fibroblast proliferation silencing by Trem2^high macrophages to prevent excessive fibrosis. We further discovered a rare population of progenitor-like cardiomyocytes after lesion, promoted by myeloid and lymphoid niche signals. Culturing non-regenerative mouse cardiomyocytes or human heart tissue with these niche factors reactivated progenitor gene expression and cell cycle activity. In summary, this spatiotemporal atlas provides valuable insights into the heterocellular interactions that control cardiac repair.

Authors with CRIS profile

Zafar Iqbal Institut für Zelluläre und Molekulare Physiologie Thomas Seidel Professur für Herz-Kreislaufphysiologie

Involved external institutions

Julius-Maximilians-Universität Würzburg

Germany (DE) Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH

Germany (DE) Technische Universität Dresden

Germany (DE)

How to cite

APA:

Chan, A.S.F., Greiner, J., Marschhäuser, L., Brennan, T.A., Perez-Feliz, S., Agrawal, A.,... Grün, D. (2025). Spatiotemporal dynamics of the cardioimmune niche during lesion repair. Nature Cardiovascular Research, 4(11), 1550-1572. https://doi.org/10.1038/s44161-025-00739-6

MLA:

Chan, Andy Shing Fung, et al. "Spatiotemporal dynamics of the cardioimmune niche during lesion repair." Nature Cardiovascular Research 4.11 (2025): 1550-1572.

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