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Proietti D, Giordani L, De Bardi M, et al. Activation of skeletal muscle-resident glial cells upon nerve injury. JCI Insight. 2021;6(7)doi: 10.1172/jci.insight.143469.
Proietti, D., Giordani, L., De Bardi, M., D'Ercole, C., Lozanoska-Ochser, B., Amadio, S., Volonté, C., Marinelli, S., Muchir, A., Bouché, M., Borsellino, G., Sacco, A., Puri, P. L., & Madaro, L. (2021). Activation of skeletal muscle-resident glial cells upon nerve injury. JCI insight, 6(7), . https://doi.org/10.1172/jci.insight.143469
Proietti, Daisy, et al. "Activation of skeletal muscle-resident glial cells upon nerve injury." JCI insight vol. 6,7 (2021). doi: https://doi.org/10.1172/jci.insight.143469
Proietti D, Giordani L, De Bardi M, D'Ercole C, Lozanoska-Ochser B, Amadio S, Volonté C, Marinelli S, Muchir A, Bouché M, Borsellino G, Sacco A, Puri PL, Madaro L. Activation of skeletal muscle-resident glial cells upon nerve injury. JCI Insight. 2021 Apr 08;6(7). doi: 10.1172/jci.insight.143469. PMID: 33661767; PMCID: PMC8119188.
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JCI Insight. 2021 Apr 08;6(7). doi: 10.1172/jci.insight.143469.

Activation of skeletal muscle-resident glial cells upon nerve injury.

JCI insight

Daisy Proietti, Lorenzo Giordani, Marco De Bardi, Chiara D'Ercole, Biliana Lozanoska-Ochser, Susanna Amadio, Cinzia Volonté, Sara Marinelli, Antoine Muchir, Marina Bouché, Giovanna Borsellino, Alessandra Sacco, Pier Lorenzo Puri, Luca Madaro

Affiliations

  1. IRCCS Fondazione Santa Lucia, Rome, Italy.
  2. Department of Anatomy, Histology, Forensic Medicine and Orthopedics, University of Rome "la Sapienza", Rome, Italy.
  3. Sorbonne Université, INSERM UMRS 974, Association Institut de Myologie, Centre de Recherche en Myologie, Paris, France.
  4. CNR, National Research Council, Institute for Systems Analysis and Computer Science, Rome, Italy.
  5. CNR, National Research Council, Institute of Biochemistry and Cell Biology, Monterotondo Scalo, Rome, Italy.
  6. Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

PMID: 33661767 PMCID: PMC8119188 DOI: 10.1172/jci.insight.143469

Abstract

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

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