Collagen VI regulates satellite cell self-renewal and muscle regeneration

Nat Commun. 2013;4:1964. doi: 10.1038/ncomms2964.

Abstract

Adult muscle stem cells, or satellite cells have essential roles in homeostasis and regeneration of skeletal muscles. Satellite cells are located within a niche that includes myofibers and extracellular matrix. The function of specific extracellular matrix molecules in regulating SCs is poorly understood. Here, we show that the extracellular matrix protein collagen VI is a key component of the satellite cell niche. Lack of collagen VI in Col6a1(-/-) mice causes impaired muscle regeneration and reduced satellite cell self-renewal capability after injury. Collagen VI null muscles display significant decrease of stiffness, which is able to compromise the in vitro and in vivo activity of wild-type satellite cells. When collagen VI is reinstated in vivo by grafting wild-type fibroblasts, the biomechanical properties of Col6a1(-/-) muscles are ameliorated and satellite cell defects rescued. Our findings establish a critical role for an extracellular matrix molecule in satellite cell self-renewal and open new venues for therapies of collagen VI-related muscle diseases.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation
  • Collagen Type VI / deficiency
  • Collagen Type VI / metabolism*
  • Elastic Modulus
  • Extracellular Space / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / transplantation
  • Fluorescent Antibody Technique
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / physiology*
  • Regeneration / physiology*
  • Satellite Cells, Skeletal Muscle / cytology*
  • Satellite Cells, Skeletal Muscle / metabolism
  • Stem Cell Niche
  • Transcription Factors / metabolism

Substances

  • Col6a1 protein, mouse
  • Collagen Type VI
  • Transcription Factors