title: Inhibition of JAK-STAT signaling stimulates adult satellite cell function.
abstract: Diminished regenerative capacity of skeletal muscle occurs during adulthood. We identified a reduction in the intrinsic capacity of mouse adult satellite cells to contribute to muscle regeneration and repopulation of the niche. Gene expression analysis identified higher expression of JAK-STAT signaling targets in 3-week [corrected] 18-month-old mice [corrected]. Knockdown of Jak2 or Stat3 significantly stimulated symmetric satellite stem cell divisions on cultured myofibers. Genetic knockdown of Jak2 or Stat3 expression in prospectively isolated satellite cells markedly enhanced their ability to repopulate the satellite cell niche after transplantation into regenerating tibialis anterior muscle. Pharmacological inhibition of Jak2 and Stat3 activity similarly stimulated symmetric expansion of satellite cells in vitro and their engraftment in vivo. Intramuscular injection of these drugs resulted in a marked enhancement of muscle repair and force generation after cardiotoxin injury. Together these results reveal age-related intrinsic properties that functionally distinguish satellite cells and suggest a promising therapeutic avenue for the treatment of muscle-wasting diseases.
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada. [3].
authors.forename: Feodor D
authors.initials: FD
authors.lastname: Price
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada. [3] [4].
authors.forename: Julia
authors.initials: J
authors.lastname: von Maltzahn
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada.
authors.forename: C Florian
authors.initials: CF
authors.lastname: Bentzinger
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Dumont
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Chang
authors.affiliation: Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.
authors.forename: David H
authors.initials: DH
authors.lastname: Wilson
authors.affiliation: Programme de Physiothérapie, Département de Réadaptation, Université Laval, Québec, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frenette
authors.affiliation: 1] Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. [2] Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D005260:Female; D055785:Gene Knockdown Techniques; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology* / Q000637:transplantation; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D053612:Janus Kinases