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

PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
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DOI:
10.1038/ncomms7364
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发表时间:
2015-03-09
影响因子:
16.6
通讯作者:
Messina, Graziella
Messina, Graziella
中科院分区:
综合性期刊1区
文献类型:
--
作者:
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

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成中膜血管细胞是血管相关祖细胞,显示出治疗肌营养不良症的治疗前景。成中膜血管细胞具有经历骨骼肌分化和穿过血管壁的能力,而不管它们被分离的发育阶段。在这里,我们表明,PW 1/Peg 3在小鼠,狗和人体组织中获得的mesoangioblasts中高水平表达,其表达水平与肌生成能力相关。沉默PW 1/Peg 3通过MyoD降解显著抑制体外成中血管细胞的肌生成潜能。此外,PW 1/Peg 3的缺乏消除了中血管母细胞穿过血管壁并通过调节连接粘附分子-A植入受损肌纤维的能力。我们的结论是,PW 1/Peg 3功能是必不可少的,赋予适当的mesoangioblast能力和PW 1/Peg 3水平的测定在人类mesoangioblast可以作为一种生物标志物,以确定最佳的供体群体的治疗应用在肌营养不良症。 中胚层成血管细胞是中胚层干细胞,由于其分化成骨骼肌的能力,具有治疗肌营养不良症的治疗潜力。这项研究表明,PW 1/Peg 3蛋白是至关重要的mesoangioblast肌和迁移的潜力,是一个治疗相关的生物标志物。
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. Mesoangioblasts are mesodermal stem cells with a therapeutic potential for treatment of muscular dystrophy due to their ability to differentiate into skeletal muscle. This study shows that the PW1/Peg3 protein is crucial for mesoangioblast myogenic and migratory potency and is a therapeutically relevant biomarker.
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