title: Human neurotrophin receptor p75NTR defines differentiation-oriented skeletal muscle precursor cells: implications for muscle regeneration.
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. p75NTR mRNA and protein are also detectable in primary myoblasts, and these levels increase transiently when cell differentiation is triggered. Transcriptome analyses of p75NTR high versus p75NTR low 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.
authors.affiliation: Neuroimmunology and Neuromuscular Disorders Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.forename: Stefania
authors.initials: S
authors.lastname: Romaggi
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.forename: Ramesh
authors.initials: R
authors.lastname: Menon
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
authors.forename: Chiara
authors.initials: C
authors.lastname: Falcone
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Paolo
authors.initials: P
authors.lastname: Confalonieri
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Cinthia
authors.initials: C
authors.lastname: Farina
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009135:Muscular Diseases / Q000473:pathology; D032446:Myoblasts / Q000502:physiology; D034622:RNA Interference; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D051017:Apoptosis Regulatory Proteins; C410727:BEX3 protein, human; D018076:DNA, Complementary