Regulation of muscle satellite cells differentiation via Rp58

• Project/Area Number: 15K15544
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ASAHARA Hiroshi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70294460)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨格筋 / サテライト細胞 / DNAメチル化 / 筋再生 / 筋分化 / Dnmt3A / Rp58 / p57Kip2 / 筋サテライト細胞

Outline of Final Research Achievements

Muscle, a power source in our musculoskeletal function, has long been studied in medicine and biology for its regeneration mechanism by tissue stem cells and transcriptional control system starting with MyoD. We identified Rp 58 as a transcription factor essential for muscle differentiation and showed that this could be responsible for muscle differentiation control in conjunction with DNA methylation. The results of this research are expected to contribute to muscle diseases and regenerative medicine.

Research Products

• [Journal Article] Dissecting the roles of miR-140 and its host gene (2018)
  • Author(s): Inui Masafumi、Mokuda Sho、Sato Tempei、Tamano Moe、Takada Shuji、Asahara Hiroshi
  • Journal Title: Nature Cell Biology Volume: 20 Issue: 5 Pages: 516-518
  • DOI: 10.1038/s41556-018-0077-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of targets of tumor suppressor microRNA-34a using a reporter library system. (2017)
  • Author(s): Ito Y, Inoue A, Seers T, Hato Y, Igarashi A, Toyama T, Taganov KD, Boldin MP, Asahara H.
  • Journal Title: Proc Natl Acad Sci USA Volume: - Issue: 15 Pages: 3927-3932
  • DOI: 10.1073/pnas.1620019114
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Analysis of transcription factors expressed at the anterior mouse limb bud (2017)
  • Author(s): Yokoyama Shigetoshi、Furukawa Soichi、Kitada Shoya、Mori Masaki、Saito Takeshi、Kawakami Koichi、Belmonte Juan Carlos Izpisua、Kawakami Yasuhiko、Ito Yoshiaki、Sato Tempei、Asahara Hiroshi
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: e0175673-e0175673
  • DOI: 10.1371/journal.pone.0175673
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tendons and Ligaments: Connecting Developmental Biology to Musculoskeletal Disease Pathogenesis (2017)
  • Author(s): Asahara Hiroshi、Inui Masafumi、Lotz Martin K
  • Journal Title: Journal of Bone and Mineral Research Volume: 32 Issue: 9 Pages: 1773-1782
  • DOI: 10.1002/jbmr.3199
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bhlha9 regulates apical ectodermal ridge formation during limb development. (2017)
  • Author(s): Kataoka K, Matsushima T, Ito Y, Sato T, Yokoyama S, Asahara H*.
  • Journal Title: JBMM. Volume: 印刷中 Issue: 1 Pages: 1-9
  • DOI: 10.1007/s00774-017-0820-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of transcription factors expressed at the anterior mouse limb bud. (2017)
  • Author(s): Yokoyama S, Furukawa S, Kitada S, Mori M, Saito T, Kawakami K, Izpisua Belmonte JC, Kawakami Y, Ito Y, Sato T, AsaharaH*.
  • Journal Title: PLoS One. Volume: 印刷中
• [Journal Article] TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes. (2017)
  • Author(s): Hasei J, Teramura T, Takehara T, Onodera Y, Horii T, Olmer M, Hatada I, Fukuda K, Ozaki T, Lotz M, Asahara H*.
  • Journal Title: Sci Rep. Volume: ７ Issue: 1 Pages: 42990-42990
  • DOI: 10.1038/srep42990
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complementary critical functions of Zfy1 and Zfy2 in mouse spermatogenesis and reproductiontran . (2017)
  • Author(s): Nakasuji T, Ogonuki N, Chiba T, Kato T, Shiozawa K, Yamatoya K, Tanaka H, Kondo T, Miyado K, Miyasaka N, Kubota T, Ogura A, Asahara H*.
  • Journal Title: PLoS Genetics. Volume: 13 Issue: 1 Pages: e1006578-e1006578
  • DOI: 10.1371/journal.pgen.1006578
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mohawk transcription factor regulates homeostasis of the periodontal ligament (2017)
  • Author(s): Koda N, Sato T, Shinohara M, Ichinose S, Ito Y, Nakamichi R, Kayama T, Kataoka K, Suzuki H, Moriyama K, Asahara H
  • Journal Title: Development Volume: 144 Pages: 313-320
  • DOI: 10.1242/dev.135798
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dnmt3a Regulates Proliferation of Muscle Satellite Cells via p57Kip2. (2016)
  • Author(s): Masashi Naito, Masaki Mori, Inagawa M, Miyata K, Hashimoto N, Tanaka S, Asahara H.
  • Journal Title: PLOS Genetics Volume: 12 Issue: 7 Pages: e1006167-e1006167
  • DOI: 10.1371/journal.pgen.1006167
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs. (2016)
  • Author(s): Rho Nakamichi, Nakamichi R, Ito Y, Inui M, Onizuka N, Kayama T, Kataoka K, Suzuki H, Mori M, Inagawa M, Ichinose S, Lotz M, Sakai D, Masuda K, Ozaki T, Asahara H.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12503-12503
  • DOI: 10.1038/ncomms12503
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene targeting of the transcription factor Mohawk in rats causes heterotropic ossification of Achilles tendon via failed tenogenesis (2016)
  • Author(s): Suzuki H, Ito Y, Shinohara M, Yamashita S, Ichinose S, Kishida A, Oyaizu T, Kayama T, Nakamichi R, Koda N, Yagishita K, Lotz MK, Okawa A, Asahara H
  • Journal Title: Proc Natl Acad Sci USA Volume: 113 Issue: 28 Pages: 7840-7845
  • DOI: 10.1073/pnas.1522054113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gtf2ird1-dependent Mohawk (Mkx) expression regulates mechanosensing properties of tendon (2016)
  • Author(s): Kayama T, Mori M, Ito Y, Matsushima T, Nakamichi R, Suzuki H, Ichinose S, Saito M, Marumo K, Asahara H
  • Journal Title: Mol Cell Biol Volume: 36 Issue: 8 Pages: 1297-309
  • DOI: 10.1128/mcb.00950-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis (2015)
  • Author(s): Gernapudi R, Wolfson B, Zhang Y, Yao Y, Yang P, Asahara H, Zhou Q
  • Journal Title: Mol Cell Biol Volume: 36 Issue: 1 Pages: 30-8
  • DOI: 10.1128/mcb.00702-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The completely automated ChIP system performed by LabDroid ”Maholo” (2018)
  • Author(s): Hiroshi Asahara
  • Organizer: Robotics and Semantic Systems for Biology (RSSB) 2
  • Int'l Joint Research / Invited
• [Presentation] Tendon development and regeneration analyzed by Mkx KO Rat (2017)
  • Author(s): 淺原弘嗣
  • Organizer: The 291st IMEG Seminar Tokyo Medical and Dental University- IMEG Joint Seminar
  • Place of Presentation: 熊本、熊本大学
  • Year and Date: 2017-02-24
• [Presentation] 腱特異的転写因子Mkxを介した腱の発生と再生 (2017)
  • Author(s): 淺原弘嗣
  • Organizer: 第56回日本生体医工学会大会
  • Invited
• [Presentation] 腱特異的転写因子Mkxの機能解析とバイオ靱帯の創出 (2017)
  • Author(s): 淺原弘嗣
  • Organizer: 第5回えひめ骨につくなる会
  • Invited
• [Presentation] 転写因子Mkxによる腱・靱帯の恒常性の制御と再生医学への応用 (2016)
  • Author(s): 淺原弘嗣
  • Organizer: 「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の開 発」武田班 班会議
  • Place of Presentation: 東京小平市、国立精神・神経医療研究センター、東京小平市
  • Year and Date: 2016-12-08
  • Invited
• [Presentation] 転写因子Mkxを基幹とした腱の発生・再生メカニズムの解明 (2016)
  • Author(s): 片岡 健輔〔ポスター発表〕, 伊藤 義晃, 千葉 朋希, 中道 亮, 加藤 眞理子, 星 菜々恵, 浅原 弘嗣
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2016-12-01
• [Presentation] LabDroid 6-site Project Group LabDroid 6-site Project Group (2016)
  • Author(s): 松島 隆英〔ポスター発表〕
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-12-01
• [Presentation] Tendon Regeneration and Development by Transcription Factor Mkx (2016)
  • Author(s): Kensuke Kataoka〔ポスター発表〕、Ysoshiaki ITO,Tomoki CHIBA,Ryo NAKAMICHI,HiroshiASAHARA
  • Organizer: Visual-JW 2016
  • Place of Presentation: 大阪、Osaka University
  • Year and Date: 2016-10-17
• [Presentation] The High-Throughput Microscopy Screening System with Genome-Wide cDNA Expression Libraries (2016)
  • Author(s): Takahide MATSUSHIMA〔ポスター発表〕、Naoki GOSHIMA,Hiroshi ASAHARA
  • Organizer: Visual-JW 2016
  • Place of Presentation: 大阪、Osaka University
  • Year and Date: 2016-10-17
• [Presentation] DNA methylationと筋分化 (2016)
  • Author(s): 淺原弘嗣
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2016-10-14
  • Invited
• [Presentation] 新規DAMPsタンパク質のスクリーニングと機能解析 (2016)
  • Author(s): 松島隆英〔ポスター発表〕、五島直樹、淺原弘嗣
  • Organizer: 第3回JCRベーシックリサーチカンファレンス
  • Place of Presentation: 千代田区、アキバプラザ内「アキバホール」
  • Year and Date: 2016-10-14
• [Presentation] リポーターライブラリーシステムによるmicroRNA-34aの標的遺伝子の同定 (2016)
  • Author(s): 伊藤義晃〔ポスター発表〕、井上敦、Timothy Seers、波戸ゆかり、五十嵐ありさ、遠山竜也、淺原弘嗣
  • Organizer: 第3回JCRベーシックリサーチカンファレンス
  • Place of Presentation: 千代田区、アキバプラザ内「アキバホール」
  • Year and Date: 2016-10-14
• [Presentation] マイクロRNA/標的遺伝子の機能的相互作用の解析と骨格パターニングにおける重要性 (2016)
  • Author(s): 佐藤天平〔ポスター発表〕、淺原弘嗣
  • Organizer: 第3回JCRベーシックリサーチカンファレンス
  • Place of Presentation: 千代田区、アキバプラザ内「アキバホール」
  • Year and Date: 2016-10-14
• [Presentation] Sox9の発言制御機構 (2016)
  • Author(s): 淺原弘嗣
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] ゲノム編集技術と医学研究・難病治療への応用 (2016)
  • Author(s): 淺原弘嗣
  • Organizer: 日本線維筋痛症学会第8回学術集会
  • Place of Presentation: 墨田区、KFCホール
  • Year and Date: 2016-09-17
  • Invited
• [Presentation] ゲノム編集技術と医学研究・難病治療への応用 (2016)
  • Author(s): 浅原弘嗣
  • Organizer: 第44回日本臨床免疫学会総会
  • Place of Presentation: 東京、京王プラザホテル
  • Year and Date: 2016-09-09
  • Invited
• [Presentation] 転写因子Mkxを基幹とした腱組織発生・再生メカニズムの解明 (2016)
  • Author(s): 片岡健輔
  • Organizer: 第17回運動器科学研究会
  • Place of Presentation: 大阪市、リーガロイヤルホテル
  • Year and Date: 2016-09-02
• [Presentation] 腱マスター転写因子Mkxはメカノストレスに応答し腱組織の恒常性を維持する (2016)
  • Author(s): 片岡健輔〔ポスター発表〕、伊藤義晃、千葉朋希、中道亮、嘉山智大、浅原弘嗣
  • Organizer: 第2回日本筋学会学術集会
  • Place of Presentation: 小平市、国立精神・神経医療研究センター教育研修棟 ユニバーサルホール
  • Year and Date: 2016-08-05
• [Presentation] Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis (2016)
  • Author(s): Hiroshi Asahara
  • Organizer: Stem Cell, Growth Factor Signaling and Bone Biology
  • Place of Presentation: 中国、杭州
  • Year and Date: 2016-07-25
  • Int'l Joint Research
• [Presentation] Mkxを介した腱・靭帯の分子ネットワークの解析と応用 (2016)
  • Author(s): 浅原弘嗣〔ポスター発表〕、伊藤義晃、千葉朋希、松島隆英、佐藤天平、片岡健輔
  • Organizer: 学際・国際的高度人材育成 ライフイノベーションマテリアル創製共同研究プロジェクト
  • Place of Presentation: 名古屋、名古屋大学 ES 館
  • Year and Date: 2016-07-08
• [Presentation] 腱組織の恒常性維持と再生の分子メカニズムの解析 (2016)
  • Author(s): 浅原弘嗣〔ポスター発表〕、片岡健輔、中道亮、鈴木英嗣、内藤昌志、望月祐輔、幸田直己、森雅樹、篠原正弘、伊藤義晃、嘉山智大
  • Organizer: 第2回日本骨免疫学会
  • Place of Presentation: 沖縄、ホテルモントレ沖縄スパ＆リゾート
  • Year and Date: 2016-07-07
• [Presentation] 脊椎動物の体軸形成においてLin28a/let-7経路はポリコーム遺伝子発現制御を介してHoxコードを調節している (2016)
  • Author(s): 佐藤天平〔ポスター発表〕、浅原弘嗣
  • Organizer: 第2回日本骨免疫学会
  • Place of Presentation: 沖縄、ホテルモントレ沖縄スパ＆リゾート
  • Year and Date: 2016-07-07
• [Presentation] 遺伝子編集技術を応用したリウマチ研究 (2016)
  • Author(s): 浅原弘嗣
  • Organizer: 千葉大学筑波大学カンファレンス
  • Place of Presentation: 東京、ベルサール八重洲
  • Year and Date: 2016-06-25
• [Presentation] MICRORNA-381 AMELIORATES ARTHRITIS BY CONTROLLING FUNCTIONS OF FIBROBLAST-LIKE SYNOVIOCYTES,WHICH ARE AFFECTED BY A TO I RNA EDITING (2016)
  • Author(s): Y.Tanaka〔ポスター発表〕, S.Takada, H.Iizasa, A.Hatzigeorgiou, S.-I.Miyazawa, T.Furumatsu, K.Nishida, H.Asahara
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: イギリス、ロンドン
  • Year and Date: 2016-06-09
• [Presentation] Bone biology (2016)
  • Author(s): 浅原弘嗣
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-04-23
• [Presentation] ゲノム編集技術とリウマチ研究への応用 (2015)
  • Author(s): 浅原弘嗣
  • Organizer: 第2回JCRベーシックリサーチカンファレンス
  • Place of Presentation: 東京大学（東京都、文京区）
  • Year and Date: 2015-10-02
• [Presentation] Skeletal development regulated at the level of RNA (2015)
  • Author(s): 浅原弘嗣
  • Organizer: 第12回Bone Biology Forum
  • Place of Presentation: クロスウェーブ幕張（千葉県、千葉市）
  • Year and Date: 2015-08-22
• [Presentation] Rp58とMkxによる筋・腱・靭帯の形成機構 (2015)
  • Author(s): 浅原弘嗣
  • Organizer: 第1回日本筋学会学術集会
  • Place of Presentation: 国立精神・神経医療研究センター（東京都、小平市）
  • Year and Date: 2015-08-08
• [Presentation] 正常な骨格筋分化には筋前駆細胞におけるde novo DNAメチル化が必要である (2015)
  • Author(s): 内藤昌志、森雅樹、田中栄、浅原弘嗣
  • Organizer: 第1回日本骨免疫学会
  • Place of Presentation: ホテルブリーズベイマリーナ（沖縄県、宮古郡）
  • Year and Date: 2015-07-01
• [Presentation] Regulation of Hox-code at RNA level during skeletal development (2015)
  • Author(s): Hiroshi Asahara
  • Organizer: The ICMRS Conference and Xiangya Osteoporsis Forum
  • Place of Presentation: the hall of Changsha Empark Grand Hotel（中国、湖南省）
  • Year and Date: 2015-04-10
  • Int'l Joint Research / Invited
• [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 システム発生・再生医学分野
  • URL: https://www.tmdusystemsbiomedicine.com/
• [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 システム発生・再生医学分野
  • URL: http://www.tmd.ac.jp/grad/syst/asahsyst/index.html