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Publication : Pten is necessary for the quiescence and maintenance of adult muscle stem cells.

First Author  Yue F Year  2017
Journal  Nat Commun Volume  8
Pages  14328 PubMed ID  28094257
Mgi Jnum  J:244565 Mgi Id  MGI:5913344
Doi  10.1038/ncomms14328 Citation  Yue F, et al. (2017) Pten is necessary for the quiescence and maintenance of adult muscle stem cells. Nat Commun 8:14328
abstractText  Satellite cells (SCs) are myogenic stem cells required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential for long-term maintenance of SCs and their regenerative function. Here we show a function of Pten (phosphatase and tensin homologue) in quiescent SCs. Deletion of Pten in quiescent SCs leads to their spontaneous activation and premature differentiation without proliferation, resulting in depletion of SC pool and regenerative failure. However, prior to depletion, Pten-null activated SCs can transiently proliferate upon injury and regenerate injured muscles, but continually decline during regeneration, suggesting an inability to return to quiescence. Mechanistically, Pten deletion increases Akt phosphorylation, which induces cytoplasmic translocation of FoxO1 and suppression of Notch signalling. Accordingly, constitutive activation of Notch1 prevents SC depletion despite Pten deletion. Our findings delineate a critical function of Pten in maintaining SC quiescence and reveal an interaction between Pten and Notch signalling.
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