Bonfanti Chiara, Rossi Giuliana, Tedesco Francesco Saverio, Giannotta Monica, Benedetti Sara, Tonlorenzi Rossana, Antonini Stefania, Marazzi Giovanna, Dejana Elisabetta, Sassoon David, Cossu Giulio, Messina Graziella
Department of BioSciences, University of Milan, 20133 Milan, Italy.
Department of Cell and Developmental Biology, University College London, 21 University Street, London WC1E 6DE, UK.
Nat Commun. 2015 Mar 9;6:6364. doi: 10.1038/ncomms7364.
Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibres through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
中胚层血管母细胞是与血管相关的祖细胞，对治疗肌肉萎缩症具有治疗前景。中胚层血管母细胞具有进行骨骼肌分化并穿越血管壁的能力，无论其在何种发育阶段被分离。在此我们表明，PW1/Peg3在从小鼠、犬类和人类组织获取的中胚层血管母细胞中高表达，其表达水平与它们的成肌能力相关。沉默PW1/Peg3通过MyoD降解显著抑制中胚层血管母细胞在体外的成肌潜能。此外，缺乏PW1/Peg3通过调节连接黏附分子A消除了中胚层血管母细胞穿越血管壁并植入受损肌纤维的能力。我们得出结论，PW1/Peg3的功能对于赋予中胚层血管母细胞适当的能力至关重要，并且测定人类中胚层血管母细胞中PW1/Peg3的水平可作为一种生物标志物，以识别用于肌肉萎缩症治疗应用的最佳供体群体。
