Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support.
Animals
Macrophages
/ metabolism
Ischemia
/ metabolism
Disease Models, Animal
Phenotype
Muscle, Skeletal
/ metabolism
Wound Healing
/ genetics
Mice, Inbred C57BL
Mice
Male
Hindlimb
/ blood supply
Neovascularization, Physiologic
/ genetics
Up-Regulation
Transcriptome
Single-Cell Analysis
Biomarkers
/ metabolism
Recovery of Function
Mice, Knockout
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Jun 2024
Jun 2024
Historique:
received:
11
11
2022
accepted:
25
04
2024
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
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 PDGFRβ. This observation was further strengthened when including unspliced transcripts in the analysis. The macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRβ 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.
Identifiants
pubmed: 39196227
doi: 10.1038/s44161-024-00478-0
pii: 10.1038/s44161-024-00478-0
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
685-700Informations de copyright
© 2024. The Author(s).
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