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.
|Number of pages||14|
|State||Published - Nov 22 2016|
Bibliographical noteFunding Information:
This work was supported by a grant from the US NIH ( R01AR060652 to S.K.) and a Purdue incentive grant from the Purdue University Office of the Vice President for Research (OVPR) to S.K. We thank Dr. YongXu Wang (University of Massachusetts Medical School) for the generous present of the Adenovirus-AdEasy overexpression system, Dr. Shuichi Sato and Dr. Ashok Kumar (University of Louisville School of Medicine) for advice on treadmill experiments, Jun Wu for mouse colony maintenance, and members of the S.K. laboratory for valuable comments.
© 2016 The Author(s)
- skeletal muscle
- stem cells
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)