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Mechanisms for the initial process of hair cell regeneration in avian inner ears

Research Project

Project/Area Number 20K09708
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKyoto University

Principal Investigator

Nakagawa Takayuki  京都大学, 医学研究科, 研究員 (50335270)

Co-Investigator(Kenkyū-buntansha) 飯田 慶  近畿大学, 理工学部, 講師 (00387961)
喜多 知子 (嶋知子)  京都大学, 医学研究科, 特定講師 (20362519)
西村 幸司  滋賀県立総合病院(臨床研究センター), その他部局等, 嘱託研究員 (20405765)
大西 弘恵  京都大学, 医学研究科, 特定助教 (50397634)
山本 典生  京都大学, 医学研究科, 准教授 (70378644)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords感音難聴 / 有毛細胞 / 再生 / 分化転換 / 鳥類
Outline of Research at the Start

哺乳類とは異なり、鳥類の聴覚器官である基底乳頭では、有毛細胞再生が自発的に誘導され、聴覚機能も再生される。鳥類とは異なり、哺乳類では有効性が期待できるレベルの聴覚機能再生は報告されていない。近年、鶏に関する遺伝子情報が充実し、網羅的遺伝子解析手法を用いて、これまで困難であった鳥類における有毛細胞再生に関連する遺伝子およびシグナルの詳細な分子生物学的解析が可能となった。鳥類における旺盛な有毛細胞再生機構を哺乳類における有毛細胞再生活性化に応用し、哺乳類蝸牛における有毛細胞再生効率を向上させ、新しい感音難聴治療薬開発につなげる。

Outline of Final Research Achievements

In contrast to mammalian cochleae, avian auditory epithelia have the capability for spontaneous regeneration of hair cells. In this project, we performed multi-omics analyses of chick hair cell regeneration processes using an explant culture model of chick auditory epithelia to explore novel methods for inducing hair cell regeneration in mammals. Bulk and single-cell RNA sequencing demonstrated involvement of IFN/JAK/STAT and TGF beta signaling in the initial process of hair cell regeneration. A pseudotime trajectory analysis indicated that supporting cells are once reprogrammed to the progenitor state before transdifferentiation into hair cells. An integrated analysis of RNA and ATAC sequencing revealed chick-specific enhancer loci of ATOH1. These findings provide novel insights for inducing hair cell regeneration in mammalian cochleae.

Academic Significance and Societal Importance of the Research Achievements

鳥類聴覚感覚上皮における有毛細胞再生に関する網羅的な遺伝子解析、特に単一細胞レベルでの解析報告は、きわめて限られており、非常に価値のあるデータリソースを獲得することができた。本研究課題で得られた知見の一部は、米国の他の研究グループの異なる実験モデルでも確認されており、信頼性の高い解析データが得られたと考える。哺乳類蝸牛での応用実験を行うためには、追加解析が必要であるが、マウス蝸牛での発生や再生誘導モデルでの解析データリソースと比較検討を進めることにより、哺乳類蝸牛有毛細胞再生に向けた新たな戦略が見いだされることが期待されるデータを獲得することができた。

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

    (15 results)

All 2023 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells2023

    • Author(s)
      Matsunaga Mami、Nakagawa Takayuki
    • Journal Title

      Pharmaceutics

      Volume: 15 Issue: 3 Pages: 777-777

    • DOI

      10.3390/pharmaceutics15030777

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium2023

    • Author(s)
      Matsunaga Mami、Yamamoto Ryosuke、Kita Tomoko、Ohnishi Hiroe、Yamamoto Norio、Okano Takayuki、Omori Koichi、Nakagawa Takayuki
    • Journal Title

      iScience

      Volume: 26 Issue: 2 Pages: 106046-106046

    • DOI

      10.1016/j.isci.2023.106046

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroprotective role of insulin-like growth factor 1 in auditory and other nervous systems2022

    • Author(s)
      Yamahara K, Yamamoto N, Kuwata F, Nakagawa T.
    • Journal Title

      Histol Histopathol

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model2020

    • Author(s)
      Matsunaga Mami、Kita Tomoko、Yamamoto Ryosuke、Yamamoto Norio、Okano Takayuki、Omori Koichi、Sakamoto Satoko、Nakagawa Takayuki
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 14 Pages: 583994-583994

    • DOI

      10.3389/fncel.2020.583994

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] EDNRB2:支持細胞から有毛細胞への再生過程における前駆細胞マーカー分子としての役割の探索2023

    • Author(s)
      松永麻美、竹内万理恵、中川隆之、大森孝一
    • Organizer
      第33回日本耳科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 鳥類蝸牛における幹細胞集団の探索と有毛細胞再生過程における役割2023

    • Author(s)
      竹内万理恵、松永麻美、中川隆之、大森孝一
    • Organizer
      第33回日本耳科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Discovering a stem cell pool in the chick auditory epithelium and its role in hair cell regeneration2023

    • Author(s)
      Takayuki Nakagawa, Marie Takeuchi, Mami Matsunaga, Ryosuke Yamamoto, Tomoko Kita, Koichi Omori
    • Organizer
      58th Inner Ear Biology Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EDNRB2: a marker gene for the intermediate cells during supporting cell-to-hair cell conversion in chick basilar papillae2023

    • Author(s)
      Mami Matsunaga, Ryosuke Yamamoto, Marie Tekeuchi, Tomoko Kita, Hiroe Ohnishi, Norio Yamamoto, Takayuki Okano, Koichi Omori, Takayuki Nakagawa
    • Organizer
      58th Inner Ear Biology Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Progenitor Cell Pools in The Chick Auditory Epithelium and Their Response to Hair Cell Loss2023

    • Author(s)
      Marie Takeuchi, Mami Matsunaga, Ryosuke Yamamoto, Tomoko Kita, Koichi Omori, Takayuki Nakagawa
    • Organizer
      47th Annual Midwinter Meeting of Association for Research in Otolaryngology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 鳥類蝸牛有毛細胞再生モデルの単一細胞遺伝子発現解析1:支持細胞分化転換過程における遺伝子発現変化2022

    • Author(s)
      中川 隆之、松永 麻美、山本 典生、大森 孝一
    • Organizer
      第32回日本耳科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 鳥類蝸牛有毛細胞再生モデルの単一細胞遺伝子発現解析2:擬似的時間変動解析による細胞運命決定機構解析2022

    • Author(s)
      松永 麻美、中川 隆之、山本 典生、大森 孝一
    • Organizer
      第32回日本耳科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Ebf1 Suppresses the Proliferation of the Cochlear Prosensory Domain and Forms the Scala Tympani and Spiral Limbus during the Development of the Inner Ear2022

    • Author(s)
      Hiroki Kagoshima, Hiroe Ohnishi, Takayuki Nakagawa, Koichi Omori, Norio Yamamoto
    • Organizer
      46th Annual MidWinter Meeting of Association for Research in Otolaryngology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-resolution transcriptional analysis of avian auditory epithelia in an explant culture model for hair cell regeneration2022

    • Author(s)
      Mami Matsunaga, Tomoko Kita, Ryosuke Yamamoto, Norio Yamamoto, Takayuki Okano, Koichi Omori, Takayuki Nakagawa
    • Organizer
      45th Annual MidWinter Meeting of Association for Research in Otolaryngology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 鳥類蝸牛有毛細胞再生初期過程の発現変動遺伝子群におけるプロモータ領域のモチーフ解析2021

    • Author(s)
      松永 麻美、喜多 知子、山本 亮介、岡野 高之、山本 典生、大森 孝一、中川 隆之
    • Organizer
      第31回日本耳科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 内耳再生研究はどこまできたのか: 30年間の 潮流の変化2020

    • Author(s)
      中川隆之
    • Organizer
      第30回日本耳科学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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