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

Shuang Liu, Shu Liu, Xinyue Wang, Jiaxi Zhou, Yujing Cao, Fei Wang, Enkui Duan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)661-674
Number of pages14
JournalAging Cell
Volume10
Issue number4
DOIs
StatePublished - Aug 2011

Keywords

  • Adult stem cells
  • Cellular senescence
  • PI3K-Akt
  • PTEN
  • Self-renewal
  • Skin-derived precursors

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro'. Together they form a unique fingerprint.

Cite this