Human neurotrophin receptor p75NTR defines differentiation-oriented skeletal muscle precursor cells: Implications for muscle regeneration

Emanuela Colombo, Stefania Romaggi, Enzo Medico, Ramesh Menon, Marina Mora, Chiara Falcone, Hanns Lochmüller, Paolo Confalonieri, Renato Mantegazza, Lucia Morandi, Cinthia Farina

Research output: Contribution to journalArticlepeer-review

Abstract

Satellite cells are resident stem cells of adult skeletal muscle that have roles in tissue repair. Although several efforts have led to the functional characterization of distinct myogenic populations in animal models, the translation of these findings to humans has been limited. Here, we analyzed the expression and function of the neurotrophin receptor p75NTR in human skeletal muscle precursor cells. We combined histological investigations of muscle biopsies with molecular and cellular analyses of primary muscle precursor cells. p75NTR is expressed by most satellite cells in vivo and is a marker for regenerating fibers in inflamed and dystrophic muscle. p75NTRhigh mRNA and protein are also detectable in primary myoblasts, and these levels increase transiently when cell differentiation is triggered. Transcriptome analyses of p75NTRhigh versus p75NTRlow muscle cells showed that p75NTR is the prototype marker for a precursor cell population that has a broad transcriptional repertoire associated with muscle development and maturation. Several in vitro experiments, including receptor blockade and gene silencing in myoblasts, proved that p75NTR specifically regulates myogenesis and dystrophin expression. Taken together, the results indicate that p75NTR is a novel marker of human differentiation-prone muscle precursor cells that is involved in myogenesis in vivo and in vitro.

Original languageEnglish
Pages (from-to)133-142
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume70
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Dystrophin
  • Myogenesis
  • Neurotrophins
  • p75NTR neurotrophin receptor
  • Regeneration
  • Satellite cell
  • Skeletal muscle

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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