title: Lkb1 deletion upregulates Pax7 expression through activating Notch signaling pathway in myoblasts.
abstract: Satellite cells play crucial roles in mediating the growth, maintenance, and repair of postnatal skeletal muscle. Activated satellite cells (myoblasts) can divide symmetrically or asymmetrically to generate progenies that self-renewal, proliferate or differentiate. Pax7 is a defining marker of quiescent and activated satellite cells, but not differentiated myoblast. We demonstrate here that deletion of Lkb1 upregulates Pax7 expression in myoblasts and inhibits asymmetric divisions that generate differentiating progenies. Furthermore, we find that Lkb1 activates the Notch signaling pathway, which subsequently increases Pax7 expression and promotes self-renewal and proliferation while inhibiting differentiation. Mechanistic studies reveal that Lkb1 regulates Notch activation through AMPK-mTOR pathway in myoblasts. Together, these results establish a key role of Lkb1 in regulating myoblast division and cell fates choices.
authors.affiliation: Department of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Animal Science, Purdue University, West Lafayette, IN 47907, USA. Electronic address: tzshan@zju.edu.cn.
authors.forename: Tizhong
authors.initials: T
authors.lastname: Shan
authors.affiliation: Department of Animal Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Animal Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Animal Science, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051763:PAX7 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051880:Receptors, Notch; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Liver kinase b1 (Lkb1); Myoblast; Notch; Pax7; Serine/threonine kinase 11 (Stk11); mTOR