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Activation mechanisms of skeletal muscle stem cells during regeneration

Research Project

Project/Area Number 16H04793
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionKyoto University

Principal Investigator

Sehara-Fujisawa Atsuko  京都大学, ウイルス・再生医科学研究所, 連携教授 (60209038)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords再生医学 / 細胞・組織 / 発生・分化 / 生体分子 / ゲノム
Outline of Final Research Achievements

We investigated factors stimulating differentiation of skeletal muscle satellite cells (SMSCs), and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes effects of hypoxia on preferential self-renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to tricarboxylic acid (TCA) cycle by producing acetyl coA from pyruvate. PDH kinase 1 is decreased under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation skeletal muscle regeneration upon injury, and aggravated pathogenesis of dystrophin-deficient mice. Thus, the metabolic flow from glycolysis to TCA cycle mediated by PDH plays a pivotal role in the efficient differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.

Academic Significance and Societal Importance of the Research Achievements

幹細胞がどのようなメカニズムで活性化され、増殖・分化するのか、という問題については、幹細胞研究が盛んな割にはわかっていない。その中にあって、最も基本的なエネルギー利用の観点から、糖代謝の変化が骨格筋幹細胞の分化に必要ということを、細胞レベル・個体レベルで示すことができ、学術的にも、医学応用的にも、非常に重要な知見を生み出すことができた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (46 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (35 results) (of which Int'l Joint Research: 10 results,  Invited: 9 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] チューリッヒ大学(スイス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] パスツール研究所(フランス)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] PDH-mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice2019

    • Author(s)
      Hori Shimpei、Hiramuki Yosuke、Nishimura Daigo、Sato Fuminori、Sehara-Fujisawa Atsuko
    • Journal Title

      The FASEB Journal

      Volume: - Issue: 7 Pages: 8094-8109

    • DOI

      10.1096/fj.201802479r

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Focal adhesions are essential to drive zebrafish heart valve morphogenesis2019

    • Author(s)
      Gunawan Felix、Gentile Alessandra、Fukuda Ryuichi、Tsedeke Ayele Taddese、Jim?nez-Amilburu Vanesa、Ramadass Radhan、Iida Atsuo、Sehara-Fujisawa Atsuko、Stainier Didier Y.R.
    • Journal Title

      The Journal of Cell Biology

      Volume: 218 Issue: 3 Pages: 1039-1054

    • DOI

      10.1083/jcb.201807175

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secretome analysis to elucidate metalloprotease-dependent ectodomain shedding of glycoproteins during neuronal differentiation2017

    • Author(s)
      Tsumagari K, Shirakabe K, Ogura M, Sato F, Ishihama Y and Sehara-Fujisawa A
    • Journal Title

      Gene to Cells

      Volume: 22(2) Issue: 2 Pages: 237-244

    • DOI

      10.1111/gtc.12466

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ADAM12-deficient zebrafish exhibit retardation in body growth at the juvenile stage without developmental defects2016

    • Author(s)
      Tokumasu Y, Iida A, Wang Z, Ansai S, Kinoshita M, Sehara-Fujisawa A
    • Journal Title

      Development, Growth & Differentiation

      Volume: 58 Issue: 4 Pages: 409-421

    • DOI

      10.1111/dgd.12286

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualization of Neuregulin 1 ectodomain shedding reveals its local processing in vitro and in vivo.2016

    • Author(s)
      Kamezaki A, Sato F, Aoki K, Asakawa K, Kawakami K, Matsuzaki F, Sehara-Fujiwara A.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 28873-28873

    • DOI

      10.1038/srep28873

    • NAID

      120005819488

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 健康に暮らす社会に向けた宇宙の活用 -基礎研究や民間の取組み2019

    • Author(s)
      瀬原淳子
    • Organizer
      国際宇宙ステーション「きぼう」利用シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Effects of Space Stay on Skeletal Muscle2019

    • Author(s)
      Atsuko Sehara-Fujisawa
    • Organizer
      International Symposium on LIVING IN SPACE 2019 From basic biology to the MOON, MARS and beyond
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The ectodomain shedding of NRG1 underlies spatial and temporal regulation of synaptogenesis and myelination of developing motor neurons2018

    • Author(s)
      F. Sato, M. Tabuchi, A. Kamezaki, A. Asakawa, K. Kawakami, A. Sehara-Fujisawa
    • Organizer
      22nd Biennial Meeting of the International Society of Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of a transcription factor 19A in the osteoblast development of sternum2018

    • Author(s)
      Mao Kuriki, Fuminori Sato, Kenta Sumiyama, Koichi Kawakami, Atsuko Sehara-Fujisawa
    • Organizer
      Joint Annual Meeting of JSDB 51st and JSCB 70th
    • Related Report
      2018 Annual Research Report
  • [Presentation] Metabolic control of skeletal muscle regeneration2018

    • Author(s)
      Shimpei Hori, Fuminori Sato, Atsuko Sehara-Fujisawa
    • Organizer
      Joint Annual Meeting of JSDB 51st and JSCB 70th
    • Related Report
      2018 Annual Research Report
  • [Presentation] The ectodomain shedding of NRG1 underlies spatial and temporal regulation of synaptogenesis and myelination of developing motor neurons2018

    • Author(s)
      F. Sato, M. Tabuchi, A. Kamezaki, A. Asakawa, K. Kawakami, A. Sehara-Fujisawa
    • Organizer
      11th meeting of the Zebrafish Disease Models Society (ZDM11)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨格筋維持における重力の役割-ゼブラフィッシュの宇宙滞在から学ぶ事2018

    • Author(s)
      瀬原淳子
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Space stay of zebrafish2018

    • Author(s)
      Atsuko Sehara
    • Organizer
      The 15th Korea-Japan Joint Seminar on Space Environment Utilization Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 人工重力発生装置を用いたゼブラフィッシュ宇宙滞在実験2018

    • Author(s)
      佐藤文規, Choi Minyong, 王梓, 今村聖実, 堀内映美, 呉泉, 藤田生水, 内田智子, 加藤充康, 谷垣文章, 東端晃, 村谷匡史, 小林純也, 高橋昭久, 菅野純夫, 松崎文雄, 鈴木穣, 川上浩一, 瀬原淳子
    • Organizer
      宇宙生物科学会第32回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゼブラフィッシュ宇宙滞在実験から微小重力の骨格筋への影響とそのメカニズムを探る2018

    • Author(s)
      佐藤文規、Choi Minyong、王梓、今村聖実、堀内映美、呉 泉、藤田 生水、内田智子、加藤 充康、谷垣文章、東端 晃、村谷匡史、小林純也、高橋昭久、菅野純夫、松崎 文雄、鈴木穣、川上浩一、瀬原淳子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Study on gravity-dependent skeletal muscle maintenance mechanisms using Zebrafish, aquatic organisms2018

    • Author(s)
      Fuminori Sato, Minyong Choi, Zi Wang, Kiyomi Imamura, Terumi Horiuchi, Wu Quan, Ikumi Fujita, Satoko Uchida, Mitsuyasu Kato, Fumiaki Tanigaki, Akira Higashibata, Masafumi Muratani, Junya Kobayashi, Akihisa Takahashi, Sumio Sugano, Fumio Matsuzaki, Yutaka Suzuki, Koichi Kawakami, Atsuko Sehara-Fujisawa
    • Organizer
      2018 ASCB EMBO Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オプトジェネティクス酸化ストレス誘導法による筋萎縮メカニズムの解明と治療薬探索2018

    • Author(s)
      佐藤文規
    • Organizer
      先進ゲノム解析研究推進プラットフォーム 拡大班会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] スパースモデリングを用いたライブイメージング技術の改善2018

    • Author(s)
      曽我部 舞奈
    • Organizer
      2018年電子情報通信学会総合大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ADAM19 restricts cardiac neural crest cells to a tenogenic fate by inhibiting chondrogenesis2018

    • Author(s)
      Hiroyuki Arai
    • Organizer
      CDB Symposium 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of a transcription factor 19A in the ossification of sternum2018

    • Author(s)
      Kuriki M, Sehara-Fujisawa A and Sato F
    • Organizer
      CDB Symposium 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Studies on skeletal muscle atrophy in space-what zebrafish experienced in a space tour2018

    • Author(s)
      Uchida, Toru Sakimura, Yasushi Kono, Masaki Shirakawa, Fumiaki Tanigaki, Masahiro Chatani, Akira Kudo, Akihisa Takahashi, Junya Kobayashi, Kiyomi Imamura, Terumi Horiuchi, Satoshi Furukawa, Tadashi Muratani, Sumio Sugano, Yutaka Suzuki, Fumio Matsuzaki, Koichi Kawakami, and Atsuko Sehara-Fujisawa
    • Organizer
      CDB Symposium 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involovement of Adam 19 in the fate decision of cadiac neural crest cells2017

    • Author(s)
      Arai H, Sato F, Yamamoto T, Kiyonari H and Sehara-Fujisawa A.
    • Organizer
      Auunal Meeting of the Japanese Society of Development Biologists
    • Related Report
      2017 Annual Research Report
  • [Presentation] Roles of a transcription factor 19A in the ossification of sternum2017

    • Author(s)
      Kuriki M, Sehara-Fujisawa A and Sato F.
    • Organizer
      Auunal Meeting of the Japanese Society of Development Biologists
    • Related Report
      2017 Annual Research Report
  • [Presentation] Visualization of Neuregulin 1 ectodomain shedding in motor neurons in zebrafish2017

    • Author(s)
      Tabuchi M, Kamezaki A, Sato F, Aoki K, Asakawa K, Kawakami K and Sehara-Fujisawa A.
    • Organizer
      Auunal Meeting of the Japanese Society of Development Biologists
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多光子顕微鏡を用いたライブイメージング技術の限界突破2017

    • Author(s)
      曽我部 舞奈
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Visualization of the Ectodomain Shedding of Neuregulin/Glial Growth Factor2017

    • Author(s)
      Atsuko Sehara-Fujisawa
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Endothelial cell-specific Integrinβ1 inhibition results reduction of vascular diameters and induction of cephalic hemorrhage2017

    • Author(s)
      Atsuo Iida, Zi Wang, Atsuko Sehara-Fujisawa
    • Organizer
      第23回小型魚類研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋維持・萎縮機構の研究:宇宙から学ぶこと2017

    • Author(s)
      瀬原 淳子
    • Organizer
      宇宙科学談話会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 筋維持・萎縮機構の研究:宇宙から学ぶこと2017

    • Author(s)
      瀬原 淳子
    • Organizer
      第6回実験動物科学シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Roles of a transcription factor 19A in the ossification of sternum2017

    • Author(s)
      Kuriki M, Sehara-Fujisawa A and Sato F
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨格筋再生の代謝制御2017

    • Author(s)
      堀 新平
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] スパースモデリングを用いたライブイメージング技術の改善2017

    • Author(s)
      曽我部 舞奈
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Live cell imaging and proteomic approaches shed light on novel aspects of ectodomain shedding in developing neurons2017

    • Author(s)
      Aosa Kamezaki, Fuminori Sato, Kazuhiro Aoki, Kazuhide Asakawa, Koichi Kawakami, Atsuko Sehara-Fujisawa
    • Organizer
      Joint Meeting of German and Japanese Society of Developmental Biologists 2017
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a fluorescent probe to monitor NRG1 ectodomain shedding in vitro and in vivo2016

    • Author(s)
      AOSA KAMEZAKI
    • Organizer
      JSDB Special Symposium:Frontier of Developmental Biology (+ 49th Meeting)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Roles of ADAM8 for skeletal muscle regeneration2016

    • Author(s)
      Daigo Nishimura , Hiroshi Sakai , Takahiko Sato , Fuminori Sato , Satoshi Nishimura ,Noriko Toyama-Sorimachi , JW. Bartsch , Atsuko Sehara-Fujisawa
    • Organizer
      第24回マクロファージ分子細胞生物学会国際シンポジウム(MMCB2016)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of Meltrin β/ADAM19 in development of the heart2016

    • Author(s)
      Atsuko Sehara-Fujisawa
    • Organizer
      Swiss-Kyoto Joint Symposium of Life Science 2016
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 幹細胞の増殖・分化制御機構のプロテアーゼ制御2016

    • Author(s)
      瀬原 淳子
    • Organizer
      第21回 日本病態プロテアーゼ学会学術集会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Establishment of a dual-fluorescence probe to visualize Neuregulin 1ectodomain shedding in developing zebrafish embryos2016

    • Author(s)
      Aosa Kamezaki, Fuminori Sato, Kazuhiro Aoki, Mai Tabuchi, Kazuhide Asakawa, Koichi Kawakami, Fumio Matsuzaki, Atsuko Sehara-Fujisawa
    • Organizer
      第22回小型魚類研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウスで肥満に関わるADAM12遺伝子のゼブラフィッシュ変異体の樹立2016

    • Author(s)
      飯田 敦夫
    • Organizer
      第2回ゼブラフィッシュ創薬研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Establishment of a fluorescence biosensor to monitor Neuregulin1 ectodomain shedding in zebrafish embryo2016

    • Author(s)
      Aosa Kamezaki
    • Organizer
      モデル動物研究会 ~ムシサカナの会@金沢~
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 画像処理装置、コンピュータプログラム及び画像補完方法2018

    • Inventor(s)
      曽我部舞奈, 大関真之, 瀬原淳子
    • Industrial Property Rights Holder
      曽我部舞奈, 大関真之, 瀬原淳子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] パースモデリングを用いて顕微鏡取得画像の情報学的補完を行うソフトウェア2017

    • Inventor(s)
      曽我部舞奈、大関真之、瀬原淳子
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] NRG1の切断検出用プローブおよびNR膜型ニューレグリンのエクトドメインシェディング可視化プローブ2016

    • Inventor(s)
      瀬原淳子、亀崎青沙、佐藤文規、青木一洋、川上浩一
    • Industrial Property Rights Holder
      瀬原淳子、亀崎青沙、佐藤文規、青木一洋、川上浩一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-01-27  

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