Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology
  • Animals
  • Cell Proliferation
  • Extracellular Matrix / metabolism
  • Fibrosis
  • Integrin beta1 / genetics
  • Keloid / pathology
  • Lectins, C-Type / analysis
  • Lectins, C-Type / metabolism
  • Lymphokines / metabolism
  • Macrophages / physiology*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Myofibroblasts / physiology*
  • Platelet-Derived Growth Factor / metabolism
  • Re-Epithelialization / genetics
  • Re-Epithelialization / physiology*
  • Skin / immunology
  • Skin / injuries*
  • Skin / pathology
  • Skin Aging / physiology
  • Transcriptome
  • Wound Healing / genetics
  • Wound Healing / physiology*


  • Integrin beta1
  • Lectins, C-Type
  • Lymphokines
  • MGL2 protein, mouse
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor C