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Study on the molecular basis that defines organ regenerative ability in an anuran amphibian (Xenopus laevis)

Research Project

Project/Area Number 20K21517
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kubo Takeo  東京大学, 大学院理学系研究科(理学部), 教授 (10201469)

Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアフリカツメガエル / 器官再生 / 再生芽 / Single cell RNA-seq / Crispr/Cas9 / Side population法 / IL-11 / マクロファージ / Crispr/cas9法 / Side population 法 / Il11 / 再生 / FGF10 / インターロイキン11 / IL11受容体 / 未分化増殖細胞 / 器官再生能 / 増殖細胞 / 成体
Outline of Research at the Start

アフリカツメガエル幼生は高い器官再生能をもつが、成体は四肢再生能をもたない。応募者は幼生尾再生芽の増殖細胞から、尾再生に必須であり、様々な組織の未分化細胞の誘導に働く因子(インターロイキン11)を同定した。ではなぜ、カエル成体は四肢再生能をもたないのか?本研究では、カエル成体切断肢の増殖細胞のトランスクリプトームを解析し、それを幼生尾増殖細胞と比較する。次いで、幼生尾再生芽の増殖細胞に比べて発現低下している遺伝子を、成体の切断肢に強制発現させることで、肢芽様構造を誘導できるか検討する。本研究は基礎生物学ばかりでなく、将来的には再生医学にも新しい視点を与える可能性がある挑戦的研究である。

Outline of Final Research Achievements

We analyzed the molecular basis and cellular dynamics to explore the molecular factors determining organ regenerative ability in Xenopus laevis tadpoles. In this research period, (1) We identified the steap4+ cell population as a candidate cell population associated with enhanced morphogenesis by FGF10 after tadpole limb bud amputation. (2) We identified immune cells able to promote larval tail regeneration and a gene essential for their function. (3) We previously showed that il11 is essential in tadpole tail regeneration. Here we showed that its receptor is also important for tail regeneration. (4) We first established and improved a knock-in method in X. laevis. (5) We established a method for enrichment and fractionation of tissue stem cells of regenerating tadpole tails by side-population method. The results of each research subject were published in international journals.

Academic Significance and Societal Importance of the Research Achievements

動物の器官再生能に関する研究は、基礎生物学のみならず、将来的には臨床応用の観点からも重要である。本研究課題の最終目標は、両生類のもつ高い器官再生能を支える両生類固有な分子基盤・細胞挙動を解明することである。本研究課題ではアフリカツメガエル幼生の肢芽切断後の形態の再形成に関与する新規な候補細胞集団の同定、尾再生に必須な新規遺伝子の同定に加えて、幼生尾再生芽からの組織幹細胞濃縮分画の単離法や、ツメガエルゲノムの任意部位へのノックイン法の確立と改善と言う、将来的な研究発展の礎となる研究基盤を整備した。これらの研究成果は何れも独自性が高く、再生生物学分野において重要な貢献をなすものと考えている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 2020 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] <i>regeneration factors expressed on myeloid</i> expression in macrophage-like cells is required for tail regeneration in <i>Xenopus laevis</i> tadpoles2023

    • Author(s)
      Deguchi Momoko、Fukazawa Taro、Kubo Takeo
    • Journal Title

      Development

      Volume: 150 Issue: 15

    • DOI

      10.1242/dev.200467

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective enrichment of stem cells in regenerating Xenopus laevis tadpole tails using the side population method2022

    • Author(s)
      Kato Sumika、Kubo Takeo、Fukazawa Taro
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 6 Pages: 290-296

    • DOI

      10.1111/dgd.12797

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular responses in the FGF10‐mediated improvement of hindlimb regenerative capacity in Xenopus laevis revealed by single‐cell transcriptomics2022

    • Author(s)
      Yanagi Nodoka、Kato Sumika、Fukazawa Taro、Kubo Takeo
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 6 Pages: 266-278

    • DOI

      10.1111/dgd.12795

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xenopus laevis il11ra.L is an experimentally proven interleukin-11 receptor component that is required for tadpole tail regeneration2022

    • Author(s)
      Suzuki Shunya、Sasaki Kayo、Fukazawa Taro、Kubo Takeo
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1903-1903

    • DOI

      10.1038/s41598-022-05954-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-temperature incubation improves both knock-in and knock-down efficiencies by the CRISPR/Cas9 system in Xenopus laevis as revealed by quantitative analysis2021

    • Author(s)
      Kato Sumika、Fukazawa Taro、Kubo Takeo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 543 Pages: 50-55

    • DOI

      10.1016/j.bbrc.2020.11.038

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of tissue stem cells and their differentiation trajectories in Xenopus tadpole tail regeneration: insights from single-cell RNA sequencing2023

    • Author(s)
      Sumika Kato, Momoko Deguchi, Takeo Kubo, Taro Fukazawa
    • Organizer
      naugural Meeting of The International Society for Regenerative Biology, Vienna, Austria
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アフリカツメガエル幼生尾の再生を促進する免疫細胞の機能に必須な因子の同定2023

    • Author(s)
      出口桃子、深澤太郎、久保健雄
    • Organizer
      第46回日本分子生物学会年会 (2023) 神戸コンベンションセンター、兵庫県神戸市
    • Related Report
      2023 Annual Research Report
  • [Presentation] Estimation of tissue stem cells and their differentiation trajectories in Xenopus tail regeneration using single-cell RNA analysis2023

    • Author(s)
      Sumika Kato, Momoko Deguchi, Takeo Kubo, Taro Fukazawa
    • Organizer
      56th Annual Meeting of the Japanese Society for Developmental Biologists (2023) 仙台国際センター、宮城県仙台市
    • Related Report
      2023 Annual Research Report
  • [Presentation] ツメガエル幼生尾再生における組織幹細胞・前駆細胞系列の解析2023

    • Author(s)
      加藤寿美香、久保健雄、深澤太郎
    • Organizer
      第46回日本分子生物学 会年会 (2023) 神戸コンベンションセンター、兵庫県神戸市
    • Related Report
      2023 Annual Research Report
  • [Presentation] ツメガエル幼生尾再生におけるシングルセル-RNA解析を用いた組織幹細胞・前駆細胞系列 の推定2023

    • Author(s)
      加藤寿美香、久保健雄、深澤太郎
    • Organizer
      日本動物学会関東支部第75回大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Side population method is effective for tissue stem cell enrichment in Xenopus laevis tadpoles.2022

    • Author(s)
      Sumika Kato, Takeo Kubo, Taro Fukazawa
    • Organizer
      The 55th Annual Meeting of the Japanese Society for Developmental Biologists
    • Related Report
      2022 Research-status Report
  • [Presentation] ツメガエル幼生尾再生に促進的に働く免疫細胞の同定2020

    • Author(s)
      出口 桃子、深澤 太郎、久保 健雄
    • Organizer
      第91回日本動物学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ツメガエル幼生尾再生に関わるIL-11受容体の機能解析2020

    • Author(s)
      鈴木 駿也、深澤 太郎、久保 健雄
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] アフリカツメガエル再生不応期の再生能低下に関わる分子機構の解析2020

    • Author(s)
      張 優希、藤倉 崇紘、深澤 太郎、久保 健雄
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Remarks] 東京大学 大学院理学系研究科 生物科学専攻 細胞生理化学研究室

    • URL

      https://www.bs.s.u-tokyo.ac.jp/~saibou/index.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] 東京大学大学院理学系研究科 生物科学専攻 細胞生理化学研究室

    • URL

      https://www.bs.s.u-tokyo.ac.jp/~saibou/

    • Related Report
      2022 Research-status Report

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Published: 2020-08-03   Modified: 2025-01-30  

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