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Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy But Age‐dependent Exhaustion of Satellite Cells
Author(s) -
Yue Feng,
Bi Pengpeng,
Wang Chao,
Li Jie,
Liu Xiaoqi,
Kuang Shihuan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.614.14
Subject(s) - pten , skeletal muscle , muscle hypertrophy , progenitor cell , stem cell , myocyte , microbiology and biotechnology , regeneration (biology) , biology , myogenesis , embryonic stem cell , satellite , anatomy , endocrinology , signal transduction , pi3k/akt/mtor pathway , genetics , gene , aerospace engineering , engineering
Skeletal muscle stem cells (satellite cells, SCs) are normally maintained in a quiescent (G 0 ) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting G Alert 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 Pten exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly, Pten ‐null SCs are predominantly in the G Alert state even in the absence of injury. The G Alert 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 G 0 ‐entry of SCs, and provide functional evidence that prolonged G Alert leads to stem cell depletion and regenerative failure. Support or Funding Information This work was supported by a grant from the US National Institutes of Health (R01AR060652 to S.K.) and Purdue incentive grant from Purdue University Office of Vice President for Research (OVPR) to S.K.