Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

Nat Commun. 2018 Sep 10;9(1):3670. doi: 10.1038/s41467-018-06068-6.


Fibro-adipogenic progenitors (FAPs) are currently defined by their anatomical position, expression of non-specific membrane-associated proteins, and ability to adopt multiple lineages in vitro. Gene expression analysis at single-cell level reveals that FAPs undergo dynamic transitions through a spectrum of cell states that can be identified by differential expression levels of Tie2 and Vcam1. Different patterns of Vcam1-negative Tie2high or Tie2low and Tie2low/Vcam1-expressing FAPs are detected during neonatal myogenesis, response to acute injury and Duchenne Muscular Dystrophy (DMD). RNA sequencing analysis identified cell state-specific transcriptional profiles that predict functional interactions with satellite and inflammatory cells. In particular, Vcam1-expressing FAPs, which exhibit a pro-fibrotic expression profile, are transiently activated by acute injury in concomitance with the inflammatory response. Aberrant persistence of Vcam1-expressing FAPs is detected in DMD muscles or upon macrophage depletion, and is associated with muscle fibrosis, thereby revealing how disruption of inflammation-regulated FAPs dynamics leads to a pathogenic outcome.

Publication types

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

MeSH terms

  • Adipogenesis / physiology*
  • Animals
  • Cell Differentiation
  • Flow Cytometry
  • Gene Expression Profiling
  • Inflammation
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Inbred mdx
  • Muscle Development / physiology*
  • Muscle, Skeletal / physiology
  • Muscular Dystrophy, Duchenne / metabolism*
  • Receptor, TIE-2 / metabolism
  • Regeneration
  • Sequence Analysis, RNA
  • Stem Cells / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Vascular Cell Adhesion Molecule-1
  • Receptor, TIE-2
  • Tek protein, mouse