title: Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells.
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 GAlertSCs 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 GAlertstate, even in the absence of an injury. The GAlertSCs 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 G0entry of SCs and provide functional evidence that prolonged GAlertleads to stem cell depletion and regenerative failure.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Bi
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003714:Denervation; D017353:Gene Deletion; D006984:Hypertrophy; D018345:Mice, Knockout; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000473:pathology; D017570:MyoD Protein; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D017570:MyoD Protein; D051059:PTEN Phosphohydrolase
keywords: Pten; aging; hypertrophy; regeneration; skeletal muscle; stem cells