Understanding of myofiber-type commitment mechanism and its neutritional control based of muscle stem cell biology

• Project/Area Number: 17H03908
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Animal production science
• Research Institution: Kyushu University
• Principal Investigator: TATSUMI RYUICHI 九州大学, 農学研究院, 教授 (40250493)
• Co-Investigator(Kenkyū-buntansha): 水野谷 航 麻布大学, 獣医学部, 准教授 (20404056) ; 古瀬 充宏 九州大学, 農学研究院, 教授 (30209176)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 筋線維型 / 遅筋型筋線維 / 筋幹細胞（衛星細胞） / Sema3A / 筋の初期成長 / アゴニスト / 食品機能性 / 食肉生産科学 / 骨格筋 / 筋幹細胞生物学 / semaphoprin 3A / 筋幹細胞(衛星細胞) / 筋細胞生物学 / 筋幹細胞 / 筋線維型制御 / 食品機能学的制御 / 食品機能学制御 / 細胞膜受容体アゴニスト / 遅筋型筋線維（抗疲労性筋線維） / semaphorin 3A (Sema3A) / 畜産物

Outline of Final Research Achievements

We very recently found that resident myogenic stem satellite cells secrete Sema3A to impact slow-fiber formation through a membrane receptor/MyoG-MEF2D/slow-MyHC signaling during muscle regeneration. Here we report that the Sema3A pathway may also work during postnatal muscle growth. In vivo experiments were conducted using satellite cell-specific Sema3A-cKO mice which received cKO treatment at 1 wk after birth and evaluation of fiber-type proportions at 15 wks. Results demonstrated that cKO mice had a drastically diminished proportion of slow fibers and a corresponding increase in fast IIb fibers. These phenotypes were supported by results from primary cultures of Sema3A-cKO cells; there were significant decreases in slow MyHC, myogenin, MEF2D, and a complementary increase in fast MyHC type IIb and total fast-MyHC. Importantly, these emerging results provide a possible contribution of dietary agonist of Sema3A receptor (including chlorogenic acid) to increasing slow-fiber population.

Academic Significance and Societal Importance of the Research Achievements

動物の出生後の初期成長期の筋線維型を制御する新奇分子機構、即ち、筋幹細胞合成・分泌因子Sema3Aに依存的なシグナリング軸(Sema3Aリガンド→細胞膜受容体neuropilin2/plexinA3複合体→ myogenin/MEF2D転写制御系→遅筋型myosin)を発見した。また、Sema3Aの細胞膜受容体を活性化する食品成分としてクロロゲン酸などを見出し、栄養機能学的に家畜・家禽の遅筋型筋線維形成を促進できる可能性を提示した。これらの研究成果は、高品質の食肉・食肉製品の生産システムの構築に資する他、健康寿命の延伸を目指す健康科学、および加齢筋医科学やスポーツ科学などにも貢献が期待される。

Research Products

• [Int'l Joint Research] University of Manitoba(カナダ)
• [Int'l Joint Research] University of Arizona(米国)
• [Int'l Joint Research] University of Manitoba(カナダ)
• [Int'l Joint Research] University of Arizona(米国)
• [Int'l Joint Research] Department of Biological Sciences/Faculty of Science/University of Manitoba(Canada)
• [Int'l Joint Research] School of Anim. & Comp. Biomed. Sci./University of Arizona(米国)
• [Journal Article] Beef extract supplementation promotes myoblast proliferation and myotube growth in C2C12 cells. (2020)
  • Author(s): Sawano S., Baba K., Sonoda Y., Wakamatsu J.-I., Tomonaga S., Furuse M., Sato Y., Tatsumi R., Ikeuchi Y., Mizunoya W.
  • Journal Title: European Journal of Nutrition Volume: - Issue: 8 Pages: 3735-3743
  • DOI: 10.1007/s00394-020-02205-4
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Gender, Rearing, and Cooking on the Metabolomic Profile of Porcine Muscles (2019)
  • Author(s): Sawano Shoko、Oza Keishi、Murakami Tetsuya、Nakamura Mako、Tatsumi Ryuichi、Mizunoya Wataru
  • Journal Title: Metabolites Volume: 10 Issue: 1 Pages: 10-10
  • DOI: 10.3390/metabo10010010
  • Peer Reviewed / Open Access
• [Journal Article] Increase in muscle endurance in mice by dietary Yamabushitake mushroom ( Hericium erinaceus ) possibly via activation of PPAR δ (2019)
  • Author(s): Komiya Yusuke、Nakamura Toshiya、Ishii Momoko、Shimizu Kuniyoshi、Hiraki Eri、Kawabata Fuminori、Nakamura Mako、Tatsumi Ryuichi、Ikeuchi Yoshihide、Mizunoya Wataru
  • Journal Title: Animal Science Journal Volume: - Issue: 6 Pages: 781-789
  • DOI: 10.1111/asj.13199
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between skeletal muscle fiber type and free amino acid levels in Japanese Black steers (2019)
  • Author(s): Mashima Daisuke、Oka Yoshiaki、Gotoh Takafumi、Tomonaga Shozo、Sawano Shoko、Nakamura Mako、Tatsumi Ryuichi、Mizunoya Wataru
  • Journal Title: Animal Science Journal Volume: 90 Issue: 4 Pages: 604-609
  • DOI: 10.1111/asj.13185
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and Purification of Satellite Cells from Young Rats by Percoll Density Gradient Centrifugation (2018)
  • Author(s): Matsuyoshi Yuji、Akahoshi Mariko、Nakamura Mako、Tatsumi Ryuichi、Mizunoya Wataru
  • Journal Title: Methods in Molecular Biology Volume: 1889 Pages: 81-93
  • DOI: 10.1007/978-1-4939-8897-6_6
  • ISBN: 9781493988969, 9781493988976
  • Peer Reviewed
• [Journal Article] Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle (2018)
  • Author(s): Sato Yusuke、Ohtsubo Hideaki、Nihei Naohiro、Kaneko Takane、Sato Yoriko、Adachi Shin-Ichi、Kondo Shinji、Nakamura Mako、Mizunoya Wataru、Iida Hiroshi、Tatsumi Ryuichi、Rada Cristina、Yoshizawa Fumiaki
  • Journal Title: FASEB Journal Volume: 32 Issue: 3 Pages: 1428-1439
  • DOI: 10.1096/fj.201700493r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluorescence microscopy data on expression of Paired Box Transcription Factor 7 in skeletal muscle of APOBEC2 knockout mice (2018)
  • Author(s): Ohtsubo Hideaki、Sato Yusuke、Matsuyoshi Yuji、Suzuki Takahiro、Mizunoya Wataru、Nakamura Mako、Tatsumi Ryuichi、Ikeuchi Yoshihide
  • Journal Title: Data in Brief Volume: 17 Pages: 1348-1351
  • DOI: 10.1016/j.dib.2018.02.063
  • Peer Reviewed / Open Access
• [Journal Article] 食品としての油脂が骨格筋の代謝特性に与える影響と筋線維タイプとの関連 (2018)
  • Author(s): 小宮佑介, 丸山アレクサンデル, 渡辺裕介, 内田直愛, 大津翔平, 小林千亜暉, 横山壱成, 鈴木貴弘, 中村真子, 辰巳隆一, 池内義秀, 水野谷航, 有原圭三
  • Journal Title: 栄養生理研究会報 Volume: 62 Pages: 9-17
  • Peer Reviewed
• [Journal Article] Fast-to-slow shift of muscle fiber-type composition by dietary apple polyphenols in rats: Impact of the low-dose supplementation (2017)
  • Author(s): Mizunoya W, Okamoto S, Miyahara H, Akahoshi M, Suzuki T, Do MKQ, Ohtsubo H, Komiya Y, Qahar M, Waga T, Nakazato K, Ikeuchi Y, Anderson JE, Tatsumi R
  • Journal Title: Animal Science Journal Volume: 88 Issue: 3 Pages: 489-499
  • DOI: 10.1111/asj.12655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] APOBEC2 negatively regulates myoblast differentiation in muscle regeneration (2017)
  • Author(s): Hideaki Ohtsubo, Yusuke Sato, Takahiro Suzuki, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi
  • Journal Title: International Journal of Biochemistry and Cell Biology Volume: 85 Pages: 91-101
  • DOI: 10.1016/j.biocel.2017.02.005
  • Peer Reviewed
• [Journal Article] Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: toward understanding the negative regulation of myoblast differentiation. (2017)
  • Author(s): Ohtsubo, H., Sato Y., Suzuki, T., Mizunoya, W., Nakamura, M., Tatsumi, R., and Ikeuchi, Y.
  • Journal Title: Data in Brief Volume: 12 Pages: 269-273
  • DOI: 10.1016/j.dib.2017.03.051
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mouse soleus (slow) and muscle shows greater intramyocellular lipid droplet accumulateon than EDL (fast) muscle: fiber type-specific analysis (2017)
  • Author(s): Komiya Y, Sawano S, Mashima D, Ichitsubo R, Nakamura M, Tatsumi R, Ikeuchi Y, Mizunoya W
  • Journal Title: Journal of Muscle Research and Cell Motility Volume: 印刷中 Issue: 2 Pages: 163-173
  • DOI: 10.1007/s10974-017-9468-6
  • Peer Reviewed / Open Access
• [Journal Article] Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cell (2017)
  • Author(s): R Tatsumi,T Suzuki, Mai-Khoi Q. Do, Y Ohya, JE. Anderson, A Shibata, M Kawaguchi, S Ohya, H Ohtsubo, W Mizunoya, S Sawano, Y Komiya, R Ichitsubo, K Ojima, S Nishimatsu, T Nohno, Y Ohsawa, Y Sunada, M Nakamura, M Furuse, Y Ikeuchi, T Nishimura, T Yagi, and R E. Allen
  • Journal Title: STEM CELLS Volume: 35 Issue: 7 Pages: 1815-1834
  • DOI: 10.1002/stem.2639
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of semaphorin 3A in myogenic regeneration and the formation of functional neuromuscular junctions on new fibers. (2016)
  • Author(s): Anderson, JE., Do, M.-K. Q., Daneshvar, N., Suzuki, T., Dort, J., Mizunoya, W., and Tatsumi, R.
  • Journal Title: Biological Review Volume: 92 Issue: 3 Pages: 1389-1405
  • DOI: 10.1111/brv.12286
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ニワトリ胚砂嚢平滑筋組織分化機構の解明 (2020)
  • Author(s): 穐本翔太・徳永亘祐・辰巳隆一・中村真子
  • Organizer: 日本家禽学会2020年度秋季大会
• [Presentation] 4種類の筋線維タイプの発現遺伝子プロファイリング (2019)
  • Author(s): 澤野 祥子、辰巳 隆一、水野谷 航
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Netrin-1 synthesized in satellite cells isolated from fast-twitch muscles may promote fast myofiber-type commitment (2019)
  • Author(s): Takahiro Suzuki, Aika Mori, Emi Ichimura, Yuriko Nishi, Rio Arimatsu, Takahiro Maeno, Ken Kobayashi, Koichi Ojima, Ryuichi Tatsumi and Takanori Nishimura
  • Organizer: The 2019 joint meeting of the American Society for Cell Biology (ASCB) and European Molecular Biology Organization (EMBO) 2019 meeting; ASCB|EMBO 2019 meeting
  • Int'l Joint Research
• [Presentation] HGF nitration abolishes myogenic stem satellite cell activation. (2019)
  • Author(s): Hirochika Kido, Nana Imatomi, Shoko Okuda, Yoshitaka Manabe, Yuji Matsuyosi, Alaa Magdi Hassanein Elgaabari, Takashi Nakashima, Shoko Sawano, Wataru Mizunoya, Mako Nakamura, and Ryuichi Tatsumi
  • Organizer: International Symposium on Agricultural, Food, Environmental and Life Sciences in Asia, 2019
  • Int'l Joint Research
• [Presentation] The serum-free media allows chick gizzard smooth muscle cells in differentiated state. (2019)
  • Author(s): Kosuke Tokunaga, Shota Akimoto, Wataru Mizunoya, Ryuichi Tatsumi and Mako Nakamura
  • Organizer: International Symposium on Agricultural, Food, Environmental and Life Sciences in Asia, 2019
  • Int'l Joint Research
• [Presentation] Improving meat quality by regulating myogenic and adipogenic cell fate -A possible role of Paired box 7 (Pax7) during adipogenic differentiation- (2019)
  • Author(s): Wakana Izumi, Yuko Takuma, Wataru Mizunoya, Ryuichi Tatsumi and Mako Nakamura
  • Organizer: International Symposium on Agricultural, Food, Environmental and Life Sciences in Asia, 2019
  • Int'l Joint Research
• [Presentation] 福岡市に生息する野生イノシシの死後硬直と行動圏に関する研究 (2019)
  • Author(s): 水野谷 航、安田 章人、西村 直人、荒川 拓実、増原 夏海、間島 大介、中村 真子、辰巳 隆一
  • Organizer: 日本畜産学会第126回大会
• [Presentation] ニワトリ胚砂嚢を用いた分化型平滑筋細胞培養法の開発 (2019)
  • Author(s): 徳永亘祐・水野谷航・辰巳隆一・中村真子
  • Organizer: 日本家禽学会2019年度秋季大会
• [Presentation] Netrin-1 synthesized in satellite cells may promote fast myofiber-type commitment during myogenic differentiation phase (2019)
  • Author(s): Takahiro Suzuki, Aika Mori, Yuriko Nishi, Rio Arimatsu, Takahiro Maeno, Ken Kobayashi, Koichi Ojima, Ryuichi Tatsumi and Takanori Nishimura
  • Organizer: Society for Muscle Biology 2019 meeting, Frontiers in myogenesis
  • Int'l Joint Research
• [Presentation] Myogenin has distinct function in satellite cells isolated from different muscles (2019)
  • Author(s): Rio Arimatsu, Yuriko Nishi, Ken Kobayashi, Ryuichi Tatsumi, Koichi Ojima, Takanori Nishimura, Takahiro Suzuki
  • Organizer: Society for Muscle Biology 2019 meeting, Frontiers in myogenesis
  • Int'l Joint Research
• [Presentation] 筋幹細胞の基礎科学とその食品機能学的制御の展望. (2019)
  • Author(s): 辰巳隆一
  • Organizer: 第１回日本体力医学会北九州地方会 教育講演
  • Invited
• [Presentation] 筋幹細胞分泌因子Sema3Aによる筋線維型制御機構の食品機能学的調節：ポリフェノールによる遅筋型筋線維形成促進 (2019)
  • Author(s): 松吉 祐児、赤星 真理子、水野谷 航、澤野 祥子、中村 真子、辰巳 隆一
  • Organizer: 日本筋学会第5回学術集会
• [Presentation] 培養基質の弾性率が筋芽細胞による自律的な筋線維型制御に与える影響 (2019)
  • Author(s): 山谷有希、有松里央、前野岳大、久江未記、小林 謙、辰巳隆一、尾嶋孝一、西邑隆徳、鈴木貴弘
  • Organizer: 日本筋学会第5回学術集会
• [Presentation] 筋幹細胞が合成するNetrin-1は速筋型筋線維の形成誘導に関与する (2019)
  • Author(s): 鈴木貴弘、森 愛華、久枝皓雅、西 百合子、有松里央、小林 謙、辰巳隆一、尾嶋孝一、西邑隆徳
  • Organizer: 日本筋学会第5回学術集会
• [Presentation] Sema3A依存的な遅筋型筋線維形成機構の食品機能学的制御： リンゴポリフェノールによる促進と活性成分の同定 (2019)
  • Author(s): 松吉祐児・赤星眞理子・大宅駿平・水野谷航・澤野祥子・中村真子・辰巳隆一
  • Organizer: 日本畜産学会第125回大会
• [Presentation] 筋幹細胞分泌因子Sema3A による遅筋型筋線維形成誘導：ヒラメ筋の損傷・再生実験による実証 (2019)
  • Author(s): 大宅駿平・松吉祐児・川口舞・水野谷航・澤野祥子・中村真子・辰巳隆一
  • Organizer: 日本畜産学会第125回大会
• [Presentation] 筋幹細胞の基礎科学とその健康・医療応用 (2019)
  • Author(s): 辰巳隆一
  • Organizer: 『九州大学』産・学・官交流促進シーズ発表会 in 東京2019
  • Invited
• [Presentation] 筋再生における筋幹細胞のHGF-Sema3A連関：more shine to myokines. (2018)
  • Author(s): 辰巳隆一
  • Organizer: 精神・神経疾患研究開発費「ジストロフィン欠損モデル動物を基盤とした筋ジストロフィーの新しい治療法開発 (主任研究者：武田伸一, 国立精神・神経医療センター 神経研究所長)」の班会議
  • Invited
• [Presentation] 筋幹細胞分泌因子による筋線維型制御 (2018)
  • Author(s): 辰巳隆一
  • Organizer: 第161回 日本獣医学会学術集会「One Health-人と動物の健康と共生」
  • Invited
• [Presentation] Percoll密度勾配遠心分離法を用いた若齢ラット由来の筋衛星細胞精製方法の確立 (2018)
  • Author(s): 松吉 祐児、赤星 真理子、中村 真子、辰巳 隆一、水野谷 航
  • Organizer: 日本筋学会第４回学術集会「筋研究の新たな地平へ-基礎と臨床の融合-」
• [Presentation] 筋成長・再生における筋幹細胞分泌因子Sema3Aの機能 (2018)
  • Author(s): 辰巳隆一
  • Organizer: 日本筋学会第４回学術集会「筋研究の新たな地平へ-基礎と臨床の融合-」
  • Invited
• [Presentation] Slow-fiber commitment by Sema3A secretion from myogenic stem satellite cells. (2018)
  • Author(s): Tatsumi R., Suzuki T., Kawaguchi M., Do M.-K. Q., Ohya S., Matsuyoshi Y., Ohya Y., Anderson J. E., Mizunoya W., Sawano S., Sakata K., Nakamura M., Allen R. E.
  • Organizer: 2018 FASEB Science Research Conference on “Skeletal Muscle Satellite Cells and Regeneration”
  • Int'l Joint Research
• [Presentation] Skeletal muscle fiber types may be regulated by multi-functional modulators secreted from satellite cells localized in each fiber. (2018)
  • Author(s): Suzuki T., Tatsumi R., Mori A., Hisaeda K., Nishi Y., Kobayashi K., Ojima K., Nishimura T.
  • Organizer: 2018 FASEB Science Research Conference on “Skeletal Muscle Satellite Cells and Regeneration”
  • Int'l Joint Research
• [Presentation] 筋幹細胞分泌因子Sema3Aによる筋線維型制御に関する研究：マウス成長過程における解析 (2018)
  • Author(s): 川口 舞、坂田拡太、松吉祐児、水野谷航、中村真子、辰巳隆一
  • Organizer: 日本畜産学会 第124回大会
• [Presentation] 衛星細胞由来のSema3Aによる遅筋型筋線維の形成誘導メカニズムの解析 (2018)
  • Author(s): 橋本 尚弥、西 百合子、森 愛華、小林 謙、辰巳 隆一、西邑 隆徳、鈴木 貴弘
  • Organizer: 日本畜産学会 第124回大会
• [Presentation] Nudt7 overexpression acyivates endogenous Nudt7 and MyHC1 mRNA expression in C2C12 myoblasts (2018)
  • Author(s): Ryo Ebihara, Wataru Mizunoya, Ryuichi Tatsumi, Mako Nakamura
  • Organizer: 日本畜産学会 第124回大会
• [Presentation] マウス骨格筋の再生に伴う筋線維タイプ組成の経時的解析 (2018)
  • Author(s): 市坪里穂、澤野祥子、辰巳隆一、中村真子、水野谷航
  • Organizer: 日本畜産学会 第124回大会
• [Presentation] Possible implication of Nudt7 in C2C12 myoblast differentiation (2017)
  • Author(s): Ebihara R., Choe S.-K., Mizunoya W., Tatsumi R., Nakamura M.
  • Organizer: International Symposium on Agricultural, Food, Environmental and Life Sciences in Asia, 2017 (AFELiSA'17)
  • Int'l Joint Research
• [Presentation] 運動による筋線維タイプの変化によって豚肉の肉質がどう変わるか？ (2017)
  • Author(s): 澤野 祥子、大座 啓史、辰巳 隆一、中村 真子、水野谷 航
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
• [Remarks] 九州大学-研究者情報
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K000315/research.html