• Open Access

The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro

Authors

  • Shuang Liu,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    2. Graduate University of the Chinese Academy of Sciences, Beijing, China
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    • These authors contribute equally to this work.

  • Shu Liu,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    2. Graduate University of the Chinese Academy of Sciences, Beijing, China
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    • These authors contribute equally to this work.

  • Xinyue Wang,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    2. Graduate University of the Chinese Academy of Sciences, Beijing, China
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  • Jiaxi Zhou,

    1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
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  • Yujing Cao,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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  • Fei Wang,

    1. Department of Cell and Developmental Biology and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
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  • Enkui Duan

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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Enkui Duan, PhD, State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China. Tel.: 86 10 64807308; fax: 86 10 64807099; e-mail: duane@ioz.ac.cn

Summary

Skin-derived precursors (SKPs) are embryonic neural crest- or somite-derived multipotent progenitor cells with properties of dermal stem cells. Although a large number of studies deal with their differentiation ability and potential applications in tissue damage repair, only a few studies have concentrated on the regulation of SKP self-renewal. Here, we found that after separation from their physiological microenvironment, human foreskin-derived SKPs (hSKPs) quickly senesced and lost their self-renewal ability. We observed a sharp decrease in Akt activity during this process, suggesting a possible role of the PI3K-Akt pathway in hSKP maintenance in vitro. Blocking this pathway with several inhibitors inhibited hSKP proliferation and sphere formation and increased hSKP senescence. In contrast, activating this pathway with PDGF-AA and a PTEN inhibitor, bpV(pic), promoted proliferation, improved sphere formation, and alleviated senescence of hSKPs, without altering their differentiation potential. Data also implied that this effect was associated with altered actions of FoxO3 and GSK-3β. Our results suggest an important role of the PI3K-Akt pathway in the senescence and self-renewal of hSKPs. These findings also provide a better understanding of the cellular mechanisms underlying hSKP self-renewal and stem cell senescence to allow more efficient expansion of hSKPs for regenerative medical applications.

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