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Gerli, Mattia Francesco Maria; Moyle, Louise Anne; Benedetti, Sara; Ferrari, Giulia; Ucuncu, Ekin; Ragazzi, Martina; Constantinou, Chrystalla; Louca, Irene; Sakai, Hiroshi; Ala, Pierpaolo; De Coppi, Paolo; Tajbakhsh, Shahragim; Cossu, Giulio; Tedesco, Francesco Saverio
Stem cell reports, 03/2019, Letnik: 12, Številka: 3Journal Article
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. Display omitted •DLL4 and PDGF-BB change satellite cell morphology, proliferation, and differentiation•DLL4 and PDGF-BB induce both perivascular and satellite cell gene expression•Treated satellite cells acquire perivascular cell properties and improved migration•Human satellite cell-derived myoblasts respond to DLL4 and PDGF-BB treatment 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.
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in: SICRIS
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