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Science. 2018 Nov 23;362(6417). pii: eaar2971. doi: 10.1126/science.aar2971.

Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair.

Author information

1
Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA. brett.shook@yale.edu valerie.horsley@yale.edu.
2
Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
3
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, USA.
4
Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 06510, USA.
5
Department of Surgery (Plastic), Yale School of Medicine, New Haven, CT 06510, USA.
6
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
7
Department of Dermatology, Atlanta Veterans Administration Health Center, Emory University, Atlanta, GA 30322, USA.
8
Department of Dermatology, Yale University, New Haven, CT 06511, USA.

Abstract

During tissue repair, myofibroblasts produce extracellular matrix (ECM) molecules for tissue resilience and strength. Altered ECM deposition can lead to tissue dysfunction and disease. Identification of distinct myofibroblast subsets is necessary to develop treatments for these disorders. We analyzed profibrotic cells during mouse skin wound healing, fibrosis, and aging and identified distinct subpopulations of myofibroblasts, including adipocyte precursors (APs). Multiple mouse models and transplantation assays demonstrate that proliferation of APs but not other myofibroblasts is activated by CD301b-expressing macrophages through insulin-like growth factor 1 and platelet-derived growth factor C. With age, wound bed APs and differential gene expression between myofibroblast subsets are reduced. Our findings identify multiple fibrotic cell populations and suggest that the environment dictates functional myofibroblast heterogeneity, which is driven by fibroblast-immune interactions after wounding.

Comment in

PMID:
30467144
DOI:
10.1126/science.aar2971

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