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© Research
Publication : Stem cell reports

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Stem cell reports - 07 Feb 2019

Gerli MFM, Moyle LA, Benedetti S, Ferrari G, Ucuncu E, Ragazzi M, Constantinou C, Louca I, Sakai H, Ala P, De Coppi P, Tajbakhsh S, Cossu G, Tedesco FS

Link to Pubmed [PMID] – 30745033

Stem Cell Reports 2019 03;12(3):461-473

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.

https://www.ncbi.nlm.nih.gov/pubmed/30745033