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Cell Rep. 2016 Nov 22;17(9):2340-2353. doi: 10.1016/j.celrep.2016.11.002.

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

Author information

1
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
2
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
3
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
4
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.

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.

KEYWORDS:

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

PMID:
27880908
PMCID:
PMC5181649
DOI:
10.1016/j.celrep.2016.11.002
[Indexed for MEDLINE]
Free PMC Article

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