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Evoking regenerative ability based on the priciple of regeneration

Research Project

Project/Area Number 16H06376
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Developmental biology
Research InstitutionNational Institute for Basic Biology (2019-2021)
Gakushuin University (2016-2018)

Principal Investigator

Agata Kiyokazu  基礎生物学研究所, 所長 (70167831)

Project Period (FY) 2016-05-31 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥177,840,000 (Direct Cost: ¥136,800,000、Indirect Cost: ¥41,040,000)
Fiscal Year 2020: ¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000)
Fiscal Year 2019: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2016: ¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Keywords四肢再生 / 関節再生 / イモリ / カエル / マウス / ディスリゼーション / インターカレーション / 再生医療 / 再生 / 関節 / 四肢 / ゲノム編集 / 四肢特異的エンハンサー / FGF / BMP / 先端化 / 発生・分化 / 器官形成 / エピゲノム
Outline of Final Research Achievements

Newt can regenerate complete limb structures after amputation including functional joint regeneration. Newt limb regeneration is achieved by two steps, distalization and intercalation. We are trying to induce limb-regeneration ability in frogs and mice. In the case of frogs, they lose the capability to achieve complete limb regeneration after metamorphosis due to the loss of MFCS1 activity after metamorphosis, although distalization is induced. When we compared the MFCS1 sequences between newts and frogs, newts were found to possess several specific sequences. Thus, we subsequently swapped the MFCS1 sequences between newts and frogs using CRISPR/Cas9 technology to evoke limb regeneration in frogs. Although we have not yet succeeded in swapping the MFCS1 sequences, we have succeeded in evoking joint regeneration in mice by artificially inducing distalization.

Academic Significance and Societal Importance of the Research Achievements

再生医療の提唱者として知られる本研究代表者が、iPS細胞を用いた再生医療ではなく、再生できる生き物から『再生の原理』を学ぶことで、再生できない生き物を再生できるようにすることを目標に研究を展開してきた。今回は、マウスで<先端化>を引き起こすことで関節再生を惹起させることに成功したことの社会的インパクトは高く、新たな再生医療へ向けて大きな前進となった。

Assessment Rating
Verification Result (Rating)

B

Assessment Rating
Result (Rating)

B: Progress in the research is delayed than the initial goal. Further efforts are necessary.

Report

(10 results)
  • 2022 Research Progress Assessment (Verification Result) ( PDF )
  • 2021 Final Research Report ( PDF )
  • 2019 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Abstract ( PDF )   Comments on the Screening Results ( PDF )   Annual Research Report
  • Research Products

    (42 results)

All 2019 2018 2017 2016 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (36 results) (of which Int'l Joint Research: 7 results,  Invited: 20 results) Remarks (3 results)

  • [Journal Article] A comprehensive reference transcriptome resource for the Iberian ribbed newt Pleurodeles waltl, an emerging model for developmental and regeneration biology2019

    • Author(s)
      Matsunami Masatoshi、Suzuki Miyuki、Haramoto Yoshikazu、Fukui Akimasa、Inoue Takeshi、Yamaguchi Katsushi、Uchiyama Ikuo、Mori Kazuki、Tashiro Kosuke、Ito Yuzuru、Takeuchi Takashi、Suzuki Ken-ichi T、Agata Kiyokazu、Shigenobu Shuji、Hayashi Toshinori
    • Journal Title

      DNA Research

      Volume: 印刷中 Issue: 3 Pages: 217-229

    • DOI

      10.1093/dnares/dsz003

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cas9 ribonucleoprotein complex allows direct and rapid analysis of coding and noncoding regions of target genes in Pleurodeles waltl development and regeneration.2018

    • Author(s)
      Suzuki M., Hayashi T*., Inoue T., Agata K., Hirayama M., Suzuki M., Shigenobu S., Takeuchi T, Yamamoto T., and Suzuki KT*.
    • Journal Title

      Developmental Biology

      Volume: 447 Issue: 2 Pages: 127-136

    • DOI

      10.1016/j.ydbio.2018.09.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatio-temporal neural stem cell behavior leads to both perfect and imperfect structural brain regeneration in adult newts.2018

    • Author(s)
      Urata Y, Yamashita W, Inoue T, Agata K.
    • Journal Title

      Biol Open.

      Volume: 7(6) Issue: 6

    • DOI

      10.1242/bio.033142

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ニワトリの関節再生に参画する細胞の探索2019

    • Author(s)
      石井維直, 松原遼, 阿形清和
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The hourglass model of limb regeneration/四肢再生の砂時計モデル2019

    • Author(s)
      Kiyokazu Agata
    • Organizer
      52nd Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The unique mmp1 expression for the stump of the joint regeneration in Xenopus laevis /アフリカツメガエル関節再生時のスタンプ領域における特異的なmmp1発現2019

    • Author(s)
      Haruka Matsubara, Kiyokazu Agata
    • Organizer
      52nd Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of the cells expected to participate in mouse joint regeneration/マウス関節再生に参画が期待される細胞の同定2019

    • Author(s)
      Masakazu Hotta, Haruka Matsubara, Kiyokazu Agata
    • Organizer
      52nd Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2019 Annual Research Report
  • [Presentation] Regenerating joint exhibits specific cellular response in the frog (Xenopus laevis)2019

    • Author(s)
      Haruka Matsubara, Kiyokazu Agata
    • Organizer
      Limb Development and Regeneration: New Tools for a Classic Model System
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 再生生物学は今、何を目指しているのか2019

    • Author(s)
      阿形清和
    • Organizer
      第2回再生学位分野融合研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] カエル(Xenopus laevis)の関節再生は特殊な細胞応答現象を示す2019

    • Author(s)
      松原遼
    • Organizer
      第2回再生学位分野融合研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] プラナリアやイモリに学ぶ再生原理と再生医療2018

    • Author(s)
      阿形清和
    • Organizer
      金沢大学 幹細胞生物学セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 再生生物学と再生医療を考える2018

    • Author(s)
      阿形清和
    • Organizer
      埼玉県高等学校生物研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regeneration, Stem Cells and Medicine2018

    • Author(s)
      Kiyokazu Agata
    • Organizer
      第70回日本細胞生物学会/第51回日本発生生物学会合同年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Differential gene expressions between joint and non-joint blastemas/stumps in frog2018

    • Author(s)
      Haruka Matsubara, Takeshi Inoue, Ei Kakuta, Kiyokazu Agata
    • Organizer
      第70回日本細胞生物学会/第51回日本発生生物学会合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 炎症、損傷治癒、再生能力の関係を考える2018

    • Author(s)
      阿形清和
    • Organizer
      第39回日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The Japanese amphibian regeneration initiative2018

    • Author(s)
      Kiyokazu Agata
    • Organizer
      Salamander Models in Cross-Disciplinary Biological Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] サラマンダー(イモリ亜目+サンショウウオ亜目)を用いた再生研究の世界潮流2018

    • Author(s)
      阿形清和
    • Organizer
      基礎生物学研究所/イベリアトゲイモリトレーニングコース
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] イベリアトゲイモリとアフリカツメガエルの再生時MMP動態解析2018

    • Author(s)
      松原遼、井上武、角田瑛、阿形清和
    • Organizer
      基礎生物学研究所/再生学異分野融合研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 両生類での四肢特異的ShhエンハンサーMFCS1に着目した四肢再生を惹起する試み2018

    • Author(s)
      角田瑛、猪鼻拓也、井上武、阿形清和
    • Organizer
      基礎生物学研究所/再生学異分野融合研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MMPに着目したマウスとイベリアトゲイモリ四肢切断時応答の差異2018

    • Author(s)
      松原遼、遠藤哲也、井上武、角田瑛、阿形清和
    • Organizer
      日本動物学会第89回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス関節再生に参画が期待される細胞の同定2018

    • Author(s)
      堀田正和、松原遼、阿形清和
    • Organizer
      日本動物学会第89回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 再生できる動物に学ぶ再生医療2018

    • Author(s)
      阿形清和
    • Organizer
      台東区教育委員会生涯学習ラーニングスクエア
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] What did we learn from regenerative animals such as planarian and newt?2018

    • Author(s)
      Kiyokzu Agata
    • Organizer
      Molecular mechanisms of developmental and regenerative biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 関節の再生を科学する2018

    • Author(s)
      阿形清和
    • Organizer
      第5回学習院大学ブランディング・シンポジウム/第24回生命科学シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Trial for elicitation of limb regeneration in frog by modifying limb-specific Shh enhancer MFCS12018

    • Author(s)
      角田瑛、猪鼻拓也、井上武、阿形清和
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] プラナリアやイモリに学ぶ再生医療2018

    • Author(s)
      阿形清和
    • Organizer
      としまコミュニティ大学
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Evoking regenerative ability from non-regenerative animals2018

    • Author(s)
      阿形清和
    • Organizer
      KEY Forum: The 3rd International Symposium on Stem Cell Traits and Developmental Systems
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Joint regeneration in newt and frog2018

    • Author(s)
      阿形清和
    • Organizer
      International Symposium at Hitrohima University ”Amphibian development, regeneration, evolution and beyond"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 再生のメカニズムをもとに将来の再生医療を考える2018

    • Author(s)
      阿形清和
    • Organizer
      広尾学園中学校・高等学校講演
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 両生類における四肢特異的shhエンハンサーMFCS1領域の転写活性の解析2017

    • Author(s)
      角田 瑛、猪鼻拓也、井上 武、阿形清和
    • Organizer
      第3回次世代両生類研究会 両生類研究に関するエトセトラ
    • Related Report
      2017 Annual Research Report
  • [Presentation] イベリアトゲイモリの四肢再生過程における再生芽サイズとパターニングの相関2017

    • Author(s)
      井上 武、木村聡介、坂本陸哉、阿形清和
    • Organizer
      第3回次世代両生類研究会 両生類研究に関するエトセトラ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 機能的な四肢再生を目指して2017

    • Author(s)
      松原 遼
    • Organizer
      第1回水棲生物再生研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 再生における傷上皮の重要性を考える2017

    • Author(s)
      阿形清和
    • Organizer
      イモリ型の臓器再生フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 再生メカニズムが語る未来の再生医療2017

    • Author(s)
      阿形清和
    • Organizer
      22世紀先端研究セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 両生類の四肢再生過程における四肢特異的shhエンハンサーMFCS1領域の解析2017

    • Author(s)
      角田 瑛、猪鼻拓也、井上 武、阿形清和
    • Organizer
      イベリアトゲイモリ研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 再生の原理を理解し、再生できないものを再生できるようにする2017

    • Author(s)
      阿形清和
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regeneration of "The Society of Cell"2017

    • Author(s)
      阿形清和
    • Organizer
      Joint Meeting of the German and Japanese Societies of Developmental Biologists
    • Place of Presentation
      Kiel大学(ドイツ・キール)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 再生できない動物を再生できるようにする2016

    • Author(s)
      阿形清和
    • Organizer
      2016年日本動物学会関東支部公開講演会 21世紀動物学の夢
    • Place of Presentation
      東京大学弥生講堂(東京都・文京区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Roles of ependymoglia cells in brain regeneration after partial excision of the amphibian optic tectum2016

    • Author(s)
      浦田悠子、山下 航、井上 武、阿形清和
    • Organizer
      the 22nd International Congress of Zoology / the 87th meeting of Zoological Society of Japan
    • Place of Presentation
      OIST/OCC(沖縄県国頭郡恩納村/宜野湾市)
    • Related Report
      2016 Annual Research Report
  • [Remarks] イベリアトゲイモリのポータルサイトiNewt

    • URL

      http://www.nibb.ac.jp/imori/main/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 学習院大学の研究室ホームページサイト

    • URL

      http://www.univ.gakushuin.ac.jp/sci./bio/laboratory/detail-agata/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 学習院大学 理学部 生命科学科 再生生物学(阿形研究室)ホームページ

    • URL

      http://www.univ.gakushuin.ac.jp/sci/bio/laboratory/detail-agata/

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-06-01   Modified: 2025-03-27  

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