title: Lkb1 is indispensable for skeletal muscle development, regeneration, and satellite cell homeostasis.
abstract: Serine/threonine kinase 11, commonly known as liver kinase b1 (Lkb1), is a tumor suppressor that regulates cellular energy metabolism and stem cell function. Satellite cells are skeletal muscle resident stem cells that maintain postnatal muscle growth and repair. Here, we used MyoD(Cre)/Lkb1(flox/flox) mice (called MyoD-Lkb1) to delete Lkb1 in embryonic myogenic progenitors and their descendant satellite cells and myofibers. The MyoD-Lkb1 mice exhibit a severe myopathy characterized by central nucleated myofibers, reduced mobility, growth retardation, and premature death. Although tamoxifen-induced postnatal deletion of Lkb1 in satellite cells using Pax7(CreER) mice bypasses the developmental defects and early death, Lkb1 null satellite cells lose their regenerative capacity cell-autonomously. Strikingly, Lkb1 null satellite cells fail to maintain quiescence in noninjured resting muscles and exhibit accelerated proliferation but reduced differentiation kinetics. At the molecular level, Lkb1 limits satellite cell proliferation through the canonical AMP-activated protein kinase/mammalian target of rapamycin pathway, but facilitates differentiation through phosphorylation of GSK-3β, a key component of the WNT signaling pathway. Together, these results establish a central role of Lkb1 in muscle stem cell homeostasis, muscle development, and regeneration.
authors: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA.
authors: Tizhong
authors: T
authors: Shan
authors: Pengpeng
authors: P
authors: Zhang
authors: Xinrong
authors: X
authors: Liang
authors: Pengpeng
authors: P
authors: Bi
authors: Feng
authors: F
authors: Yue
authors: Shihuan
authors: S
authors: Kuang
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006706:Homeostasis / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases
keywords: Liver kinase b1; Myogenesis; Serine/threonine kinase 11; Stem cells