Activation of skeletal muscle-resident glial cells upon nerve injury

JCI Insight. 2021 Apr 8;6(7):e143469. doi: 10.1172/jci.insight.143469.


Here, we report on the identification of Itga7-expressing muscle-resident glial cells activated by loss of neuromuscular junction (NMJ) integrity. Gene expression analysis at the bulk and single-cell level revealed that these cells are distinct from Itga7-expressing muscle satellite cells. We show that a selective activation and expansion of Itga7+ glial cells occur in response to muscle nerve lesion. Upon activation, muscle glial-derived progenies expressed neurotrophic genes, including nerve growth factor receptor, which enables their isolation by FACS. We show that activated muscle glial cells also expressed genes potentially implicated in extracellular matrix remodeling at NMJs. We found that tenascin C, which was highly expressed by muscle glial cells, activated upon nerve injury and preferentially localized to NMJ. Interestingly, we observed that the activation of muscle glial cells by acute nerve injury was reversible upon NMJ repair. By contrast, in a mouse model of ALS, in which NMJ degeneration is progressive, muscle glial cells steadily increased over the course of the disease. However, they exhibited an impaired neurotrophic activity, suggesting that pathogenic activation of glial cells may be implicated in ALS progression.

Keywords: Muscle Biology; Neuromuscular disease; Skeletal muscle.

Publication types

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

MeSH terms

  • Amyotrophic Lateral Sclerosis / pathology*
  • Animals
  • Antigens, CD / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Integrin alpha Chains / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Skeletal / cytology*
  • Myelin Proteolipid Protein / genetics
  • Myelin Proteolipid Protein / metabolism
  • Neuroglia / cytology
  • Neuroglia / physiology*
  • Neuromuscular Junction / cytology
  • Receptor, Nerve Growth Factor / genetics
  • Receptors, Cholinergic / metabolism
  • Sciatic Nerve / injuries
  • Single-Cell Analysis
  • Spinal Cord Injuries / pathology*
  • Superoxide Dismutase-1 / genetics


  • Antigens, CD
  • Integrin alpha Chains
  • Myelin Proteolipid Protein
  • Plp1 protein, mouse
  • Receptor, Nerve Growth Factor
  • Receptors, Cholinergic
  • SOD1 protein, human
  • integrin alpha7
  • Superoxide Dismutase-1