PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence

被引:39
作者
Bonfanti, Chiara [1 ]
Rossi, Giuliana [1 ]
Tedesco, Francesco Saverio [2 ]
Giannotta, Monica [3 ]
Benedetti, Sara [2 ,4 ]
Tonlorenzi, Rossana [5 ]
Antonini, Stefania [1 ]
Marazzi, Giovanna [6 ]
Dejana, Elisabetta [1 ,3 ]
Sassoon, David [6 ]
Cossu, Giulio [1 ,2 ,7 ]
Messina, Graziella [1 ]
机构
[1] Univ Milan, Dept Biosci, I-20133 Milan, Italy
[2] UCL, Dept Cell & Dev Biol, London WC1E 6DE, England
[3] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy
[4] UCL, Inst Child Hlth, London WC1N 1EH, England
[5] Hosp San Raffaele, Div Neurosci INSPE, I-20132 Milan, Italy
[6] Univ Paris 06, INSERM, Sorbonne Univ, Stem Cells & Regenerat Med,ICAN UMRS 1166, F-75634 Paris, France
[7] Univ Manchester, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
基金
欧洲研究理事会; 英国医学研究理事会;
关键词
SKELETAL-MUSCLE; IMPRINTED GENE; MYOD; DIFFERENTIATION; PROGENITOR; MYOGENESIS; ADHESION; DISTINCT; THERAPY; PW1;
D O I
10.1038/ncomms7364
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:13
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