Regeneration of fat cells from myofibroblasts during wound healing

Science. 2017 Feb 17;355(6326):748-752. doi: 10.1126/science.aai8792. Epub 2017 Jan 5.

Abstract

Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.

Publication types

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

MeSH terms

  • Adipocytes / physiology*
  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Morphogenetic Protein 4 / pharmacology
  • Bone Morphogenetic Proteins / metabolism
  • Cells, Cultured
  • Cellular Reprogramming*
  • Cicatrix / pathology
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / pathology
  • Hair Follicle / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Myofibroblasts / drug effects
  • Myofibroblasts / physiology*
  • Recombinant Proteins / pharmacology
  • Regeneration*
  • Signal Transduction
  • Transcription Factors / metabolism
  • Wound Healing*

Substances

  • BMP2 protein, human
  • BMP4 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Ebfaz protein, mouse
  • Recombinant Proteins
  • Transcription Factors