Spatiotemporal dynamics of the cardioimmune niche during lesion repair
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<sup>high</sup> 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
- Thomas Seidel (ORCID: https://orcid.org/0000-0002-3127-1693)
- Tamara Vico (ORCID: https://orcid.org/0000-0002-5428-688X)
- Franziska Schneider‐Warme (ORCID: https://orcid.org/0000-0002-5873-9436)
- Zafar Iqbal (ORCID: https://orcid.org/0000-0002-9206-7792)
- Ingo Hilgendorf (ORCID: https://orcid.org/0000-0002-0024-1643)
- Peter Karl Kohl (ORCID: https://orcid.org/0000-0003-0416-6270)
- Eva A. Rog‐Zielinska
- Jennifer Wing Lam Cheung
- Martin Vaeth (ORCID: https://orcid.org/0000-0001-8974-7052)
- Joachim Greiner (ORCID: https://orcid.org/0000-0001-5454-2962)
- Alexander Klesen (ORCID: https://orcid.org/0000-0001-8893-8287)
- Julieta Aprea (ORCID: https://orcid.org/0000-0002-8749-7878)
- Dominic Grün (ORCID: https://orcid.org/0000-0002-3364-5898)
- Helene Hemmer
- Ankit Agrawal (ORCID: https://orcid.org/0009-0006-1700-2397)
- Andy Chan (ORCID: https://orcid.org/0000-0002-1170-8085)
- Tomás A. Brennan
- Stefanie Perez‐Feliz (ORCID: https://orcid.org/0009-0009-2880-2367)
- Lisa Marschhäuser
- Katrin Sinning (ORCID: https://orcid.org/0009-0004-5841-2398)
Institutions
- University of Freiburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Würzburg (DE)
- University Medical Center Freiburg (DE)
- Universitäts-Herzzentrum Freiburg-Bad Krozingen (DE)
- Center for Systems Biology Dresden (DE)
Publication Details
- Journal
- Nature Cardiovascular Research
- Published
- 2025-11-03
- DOI
- https://doi.org/10.1038/s44161-025-00739-6
- Citations
- 3
- Primary Topic
- Cardiac Fibrosis and Remodeling
- Type
- article
- Field-Weighted Citation Impact
- 4.16