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

Author

Listed:
  • 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
    Purdue University)

  • Timothy L. Ratliff

    (Center for Cancer Research, Purdue University
    Purdue University)

  • Timothy P. Gavin

    (Purdue University)

  • Shihuan Kuang

    (Purdue University, 901 W State Street
    Center for Cancer Research, Purdue University)

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.

Suggested Citation

  • Feng Yue & Pengpeng Bi & Chao Wang & Tizhong Shan & Yaohui Nie & Timothy L. Ratliff & Timothy P. Gavin & Shihuan Kuang, 2017. "Pten is necessary for the quiescence and maintenance of adult muscle stem cells," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14328
    DOI: 10.1038/ncomms14328
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    Cited by:

    1. Jiamin Qiu & Feng Yue & Peipei Zhu & Jingjuan Chen & Fan Xu & Lijia Zhang & Kun Ho Kim & Madigan M. Snyder & Nanjian Luo & Hao-wei Xu & Fang Huang & W. Andy Tao & Shihuan Kuang, 2023. "FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Suyang Zhang & Feng Yang & Yile Huang & Liangqiang He & Yuying Li & Yi Ching Esther Wan & Yingzhe Ding & Kui Ming Chan & Ting Xie & Hao Sun & Huating Wang, 2023. "ATF3 induction prevents precocious activation of skeletal muscle stem cell by regulating H2B expression," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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