title: Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency.
abstract: When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic 'scaling' of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a 'normal' quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1-expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determines initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration and ameliorating muscle pathology.
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, United States.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Southard
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, United States.|School of Medicine, University of Missouri, Columbia, United States.|Department of Biomedical Sciences, University of Missouri, Columbia, United States.|College of Veterinary Medicine, University of Missouri, Columbia, United States.
authors.forename: Ju-Ryoung
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, United States.
authors.forename: SiewHui
authors.initials: S
authors.lastname: Low
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, United States.|School of Medicine, University of Missouri, Columbia, United States.|Department of Biomedical Sciences, University of Missouri, Columbia, United States.|College of Veterinary Medicine, University of Missouri, Columbia, United States.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsika
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, United States.
authors.forename: Christoph
authors.identifier: 0000-0002-6466-0820
authors.initials: C
authors.lastname: Lepper
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D016189:Dystrophin / Q000172:deficiency*; D015870:Gene Expression; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D016189:Dystrophin; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors
keywords: developmental biology; mouse; muscular dystrophy; regeneration; satellite cell; skeletal muscle; stem cells