Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells

Feng Yue, Pengpeng Bi, Chao Wang, Jie Li, Xiaoqi Liu, Shihuan Kuang

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G0) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting GAlert SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly, Pten null SCs are predominantly in the GAlert state, even in the absence of an injury. The GAlert SCs are deficient in self-renewal and subjected to accelerated depletion during regeneration and aging and fail to repair muscle injury in old mice. Our findings demonstrate a key requirement of Pten in G0 entry of SCs and provide functional evidence that prolonged GAlert leads to stem cell depletion and regenerative failure.

Original languageEnglish
Pages (from-to)2340-2353
Number of pages14
JournalCell Reports
Volume17
Issue number9
DOIs
StatePublished - Nov 22 2016

Bibliographical note

Publisher Copyright:
© 2016 The Author(s)

Keywords

  • Pten
  • aging
  • hypertrophy
  • regeneration
  • skeletal muscle
  • stem cells

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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