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Summary of Nature Cardiovascular Research, https://doi.org/10.1038/s44161-025-00739-6
Dr. Andy Shing-Fung Chan et al.
Points
- Integrated single-cell RNA sequencing and high-resolution spatial transcriptomics were used to reconstruct fibrotic niche spatiotemporal dynamics after cardiac injury in adult mice.
- A complex multicellular network regulating cardiac repair was revealed, including fibroblast proliferation silencing by Trem2high macrophages to prevent excessive fibrosis.
- A rare population of progenitor-like cardiomyocytes was discovered after lesion, promoted by myeloid and lymphoid niche signals within the cardiac environment.
- Culturing non-regenerative mouse cardiomyocytes or human heart tissue with niche factors reactivated progenitor gene expression and cell cycle activity.
- This spatiotemporal atlas provides valuable insights into the heterocellular interactions that control cardiac repair and regeneration mechanisms.
Summary
The research reconstructs the spatiotemporal dynamics of the fibrotic niche following cardiac injury in adult mice, utilizing an integrated approach of single-cell RNA sequencing and high-resolution spatial transcriptomics to map the molecular events of cardiac wound healing. This methodology established a comprehensive cellular and molecular atlas detailing the heterocellular interactions that regulate post-myocardial injury repair. A central finding identifies a complex multicellular network, where a specific subset of Trem2high macrophages plays a critical role in modulating the repair process by actively suppressing fibroblast proliferation, a mechanism hypothesized to mitigate pathological scar formation and prevent excessive cardiac fibrosis.
The investigation further delineated the cellular environment by identifying a rare, post-lesion population of progenitor-like cardiomyocytes. The emergence and propagation of these regenerative cells were found to be critically dependent on paracrine signals derived from the local myeloid and lymphoid niche compartments. This observation suggests that the immune and stromal components of the wound environment function synergistically to promote a regenerative phenotype within the ordinarily non-regenerative adult myocardium.
To confirm the therapeutic potential of the identified niche signals, non-regenerative mouse cardiomyocytes and human heart tissue samples were cultured in vitro with the myeloid and lymphoid niche factors. Exposure to these factors successfully reactivated progenitor gene expression and restored cell cycle activity in both the murine and human cardiac tissue models. In summary, this comprehensive spatiotemporal reconstruction provides valuable molecular and cellular targets for novel regenerative strategies aimed at improving cardiac function following ischemic tissue damage.
Link to the article: https://www.nature.com/articles/s44161-025-00739-6
References
Chan, A. S.-F., Greiner, J., Marschhäuser, L., Brennan, T. A., Perez-Feliz, S., Agrawal, A., Hemmer, H., Sinning, K., Cheung, J. W. L., Iqbal, Z., Klesen, A., Vico, T. A., Aprea, J., Hilgendorf, I., Seidel, T., Vaeth, M., Rog-Zielinska, E. A., Kohl, P., Schneider-Warme, F., & Grün, D. (2025). Spatiotemporal dynamics of the cardioimmune niche during lesion repair. Nature Cardiovascular Research, 1–23. https://doi.org/10.1038/s44161-025-00739-6
