title: Muscle stem cell fate is controlled by the cell-polarity protein Scrib.
abstract: Satellite cells are resident skeletal muscle stem cells that supply myonuclei for homeostasis, hypertrophy, and repair in adult muscle. Scrib is one of the major cell-polarity proteins, acting as a potent tumor suppressor in epithelial cells. Here, we show that Scrib also controls satellite-cell-fate decisions in adult mice. Scrib is undetectable in quiescent cells but becomes expressed during activation. Scrib is asymmetrically distributed in dividing daughter cells, with robust accumulation in cells committed to myogenic differentiation. Low Scrib expression is associated with the proliferative state and preventing self-renewal, whereas high Scrib levels reduce satellite cell proliferation. Satellite-cell-specific knockout of Scrib in mice causes a drastic and insurmountable defect in muscle regeneration. Thus, Scrib is a regulator of tissue stem cells, controlling population expansion and self-renewal with Scrib expression dynamics directing satellite cell fate.
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. Electronic address: yusuke-ono@nagasaki-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Teikyo University, Tokyo 173-8605, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Cell Cycle and Cancer Genetics, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Pathology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Molecular Biology and Biochemistry, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Humbert
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.affiliation: Kings College London, Randall Division of Cellular and Molecular Biophysics, London SE1 1UL, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Zammit
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology; D017570:MyoD Protein / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017570:MyoD Protein; D051763:PAX7 Transcription Factor; C057363:MyoD1 myogenic differentiation protein; C497322:Pax7 protein, mouse; C508433:scrib protein, mouse