Stem Cell Reports (Mar 2019)

Combined Notch and PDGF Signaling Enhances Migration and Expression of Stem Cell Markers while Inducing Perivascular Cell Features in Muscle Satellite Cells

  • Mattia Francesco Maria Gerli,
  • Louise Anne Moyle,
  • Sara Benedetti,
  • Giulia Ferrari,
  • Ekin Ucuncu,
  • Martina Ragazzi,
  • Chrystalla Constantinou,
  • Irene Louca,
  • Hiroshi Sakai,
  • Pierpaolo Ala,
  • Paolo De Coppi,
  • Shahragim Tajbakhsh,
  • Giulio Cossu,
  • Francesco Saverio Tedesco

Journal volume & issue
Vol. 12, no. 3
pp. 461 – 473

Abstract

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Summary: Satellite cells are responsible for skeletal muscle regeneration. Upon activation, they proliferate as transient amplifying myoblasts, most of which fuse into regenerating myofibers. Despite their remarkable differentiation potential, these cells have limited migration capacity, which curtails clinical use for widespread forms of muscular dystrophy. Conversely, skeletal muscle perivascular cells have less myogenic potential but better migration capacity than satellite cells. Here we show that modulation of Notch and PDGF pathways, involved in developmental specification of pericytes, induces perivascular cell features in adult mouse and human satellite cell-derived myoblasts. DLL4 and PDGF-BB-treated cells express markers of perivascular cells and associate with endothelial networks while also upregulating markers of satellite cell self-renewal. Moreover, treated cells acquire trans-endothelial migration ability while remaining capable of engrafting skeletal muscle upon intramuscular transplantation. These results extend our understanding of muscle stem cell fate plasticity and provide a druggable pathway with clinical relevance for muscle cell therapy. : Gerli and Moyle and colleagues show that treatment with molecules involved in developmental specification of pericytes (DLL4 and PDGF-BB) alters satellite cell fate and provides them with features potentially relevant for novel cell therapy protocols. Keywords: muscle stem cells, satellite cells, stem cell fate, reprogramming, perivascular cells, muscle regeneration, muscular dystrophy, cell therapy, NOTCH, PDGF