Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells. (31st May 2017)

• Record Type: Journal Article
• Authors: Tatsumi, Ryuichi; Suzuki, Takahiro; Do, Mai-Khoi Q.; Ohya, Yuki; Anderson, Judy E.; Shibata, Ayumi; Kawaguchi, Mai; Ohya, Shunpei; Ohtsubo, Hideaki; Mizunoya, Wataru; Sawano, Shoko; Komiya, Yusuke; Ichitsubo, Riho; Ojima, Koichi; Nishimatsu, Shin-ichiro; Nohno, Tsutomu; Ohsawa, Yutaka; Sunada, Yoshihide; Nakamura, Mako; Furuse, Mitsuhiro; Ikeuchi, Yoshihide; Nishimura, Takanori; Yagi, Takeshi; Allen, Ronald E.
• Is Part Of: Stem cells. Volume 35:Number 7(2017:Jul.)
• Page Start: 1815
• Page End: 1834
• Publication Date: 2017-05-31
• Subjects: Resident myogenic stem satellite cells -- Semaphorin 3A -- Myogenin -- Slow-twitch myofiber -- Muscle endurance -- Regeneration; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2639
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression. Importantly, satellite cell-specific Sema3A conditional-knockout adult mice (Pax7CreER T2 -Sema3A fl ° x activated by tamoxifen-i.p. injection) provided direct in vivo evidence for the Sema3A-driven program, by showing that slow-fiber generation and muscle endurance were diminished after repair from cardiotoxin-injury of gastrocnemius muscle. Overall, the findings highlight an active role for satellite cell-secreted Sema3A ligand as a key "commitment factor" for the slow-fiber population during muscle regeneration. Results extend our understanding of the myogenic stem-cell strategy that regulates fiber-type differentiation and is responsible for skeletal muscle contractility, energy metabolism, fatigue resistance, and its susceptibility to aging and disease.