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

Feng Yue, Pengpeng Bi, Chao Wang, Tizhong Shan, Yaohui Nie, Timothy L. Ratliff, Timothy P. Gavin and Shihuan Kuang ()
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Feng Yue: Purdue University, 901 W State Street
Pengpeng Bi: Purdue University, 901 W State Street
Chao Wang: Purdue University, 901 W State Street
Tizhong Shan: Purdue University, 901 W State Street
Yaohui Nie: Purdue University, 901 W State Street
Timothy L. Ratliff: Center for Cancer Research, Purdue University
Timothy P. Gavin: Purdue University
Shihuan Kuang: Purdue University, 901 W State Street

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14328

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