Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation.

Aging / physiology Angiotensin II / administration & dosage Animals Arteries / cytology Arteritis / immunology Bone Marrow / physiology Bone Marrow Transplantation Cell Differentiation / physiology Cell Lineage Disease Models, Animal Female Hematopoietic Stem Cells / physiology Homeostasis / physiology Humans Macrophages / physiology Male Mice Mice, Transgenic RNA-Seq Regeneration / physiology Single-Cell Analysis Transplantation Chimera

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
11 09 2020

Historique:

received: 24 10 2019

accepted: 12 08 2020

entrez: 12 9 2020

pubmed: 13 9 2020

medline: 2 10 2020

Statut: epublish

Résumé

Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.

Identifiants

DOI: 10.1038/s41467-020-18287-x PMID: 32917889 PMC: PMC7486394

pubmed: 32917889

doi: 10.1038/s41467-020-18287-x

pii: 10.1038/s41467-020-18287-x

pmc: PMC7486394

doi:

Substances chimiques

Angiotensin II 11128-99-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

4549

Subventions

Organisme : Howard Hughes Medical Institute

Pays : United States

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