title: Pten is necessary for the quiescence and maintenance of adult muscle stem cells.
abstract: Satellite cells (SCs) are myogenic stem cells required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential for long-term maintenance of SCs and their regenerative function. Here we show a function of Pten (phosphatase and tensin homologue) in quiescent SCs. Deletion of Pten in quiescent SCs leads to their spontaneous activation and premature differentiation without proliferation, resulting in depletion of SC pool and regenerative failure. However, prior to depletion, Pten-null activated SCs can transiently proliferate upon injury and regenerate injured muscles, but continually decline during regeneration, suggesting an inability to return to quiescence. Mechanistically, Pten deletion increases Akt phosphorylation, which induces cytoplasmic translocation of FoxO1 and suppression of Notch signalling. Accordingly, constitutive activation of Notch1 prevents SC depletion despite Pten deletion. Our findings delineate a critical function of Pten in maintaining SC quiescence and reveal an interaction between Pten and Notch signalling.
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Bi
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.
authors.forename: Tizhong
authors.identifier: 0000-0002-4738-414X
authors.initials: T
authors.lastname: Shan
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.|Department of Health and Kinesiology, Purdue University, 800 W. Stadium Ave, West Lafayette, Indiana 47907, USA.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Center for Cancer Research, Purdue University, 201 S University Street, West Lafayette, Indiana 47907, USA.|Department of Comparative Pathobiology, Purdue University, 625 Harrison St, West Lafayette, Indiana 47907, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
authors.affiliation: Department of Health and Kinesiology, Purdue University, 800 W. Stadium Ave, West Lafayette, Indiana 47907, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Gavin
authors.affiliation: Department of Animal Sciences, Purdue University, 901 W State Street, West Lafayette, Indiana 47907, USA.|Center for Cancer Research, Purdue University, 201 S University Street, West Lafayette, Indiana 47907, USA.
authors.forename: Shihuan
authors.identifier: 0000-0001-9180-3180
authors.initials: S
authors.lastname: Kuang
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D016922:Cellular Senescence; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism
chemical_list: D000071161:Forkhead Box Protein O1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse