| First Author | Amoedo-Leite C | Year | 2024 |
| Journal | Nat Cardiovasc Res | Volume | 3 |
| Issue | 6 | Pages | 685-700 |
| PubMed ID | 39196227 | Mgi Jnum | J:358638 |
| Mgi Id | MGI:7782714 | Doi | 10.1038/s44161-024-00478-0 |
| Citation | Amoedo-Leite C, et al. (2024) Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support. Nat Cardiovasc Res 3(6):685-700 |
| abstractText | Sterile inflammation after injury is important for tissue restoration. In injured human and mouse tissues, macrophages were recently found to accumulate perivascularly. This study investigates if macrophages adopt a mural cell phenotype important for restoration after ischemic injury. Single-cell RNA sequencing of fate-mapped macrophages from ischemic mouse muscles demonstrates a macrophage-toward-mural cell switch of a subpopulation of macrophages with downregulated myeloid cell genes and upregulated mural cell genes, including PDGFRbeta. This observation was further strengthened when including unspliced transcripts in the analysis. The macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRbeta deficiency prevented their perivascular macrophage phenotype, impaired vessel maturation and increased vessel leakiness, which ultimately reduced limb function. In conclusion, macrophages in adult ischemic tissue were demonstrated to undergo a cellular program to morphologically, transcriptomically and functionally resemble mural cells while weakening their macrophage identity. The macrophage-to-mural cell-like phenotypic switch is crucial for restoring tissue function and warrants further exploration as a potential target for immunotherapies to enhance healing. |
