Macrophages fine tune satellite cell fate in dystrophic skeletal muscle of mdx mice

PLoS Genet. 2019 Oct 18;15(10):e1008408. doi: 10.1371/journal.pgen.1008408. eCollection 2019 Oct.

Abstract

Satellite cells (SCs) are muscle stem cells that remain quiescent during homeostasis and are activated in response to acute muscle damage or in chronic degenerative conditions such as Duchenne Muscular Dystrophy. The activity of SCs is supported by specialized cells which either reside in the muscle or are recruited in regenerating skeletal muscles, such as for instance macrophages (MΦs). By using a dystrophic mouse model of transient MΦ depletion, we describe a shift in identity of muscle stem cells dependent on the crosstalk between MΦs and SCs. Indeed MΦ depletion determines adipogenic conversion of SCs and exhaustion of the SC pool leading to an exacerbated dystrophic phenotype. The reported data could also provide new insights into therapeutic approaches targeting inflammation in dystrophic muscles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Disease Models, Animal
  • Dystrophin / genetics
  • Humans
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred mdx
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Myoblasts / metabolism
  • Regeneration / genetics*
  • Satellite Cells, Skeletal Muscle / metabolism
  • Satellite Cells, Skeletal Muscle / pathology

Substances

  • Dystrophin

Grants and funding

The work in F. De Santa laboratory was supported by Duchenne Parent Project-Netherlands (DPP-NL; Grant # DeSanta-DPP-NL) to F.D.S., https://duchenne.nl; Association Francaise contre les Myopathies (AFM Telethon; Grant # 16772) to F.D.S., http://www.afm-telethon.com; Italian Ministry of Education, and Universities and Research (MIUR; Grant: IRMI CTN01_00177_888744) to F.D.S., www.miur.gov.it. L.Madaro was supported by AFM (Fellowship #16805), http://www.afm-telethon.com and by Italian Ministry of Health (Grant: GR- 2013-02356592), www.salute.gov.it. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.