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The establishment of intercellular co-ordination of ciliary movement by using human iPS cell-derived airway epithelial cells

Research Project

Project/Area Number 17K17853
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Experimental pathology
Research InstitutionOsaka University

Principal Investigator

Konishi Satoshi  大阪大学, 医学系研究科, 特任研究員 (10789564)

Research Collaborator Tsukita Sachiko  大阪大学, 生命機能研究科, 教授 (00188517)
Gotoh Shimpei  京都大学, 大学院医学研究科, 特定准教授 (50747219)
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords多繊毛協調運動 / 粘液繊毛クリアランス / 気道疾患モデリング / ヒトiPS細胞 / 初代培養マウス気管上皮細胞 / ライブセルイメージング / 気道繊毛上皮細胞 / 超解像顕微鏡 / 平面極性コア蛋白 / アピカル細胞骨格 / 疾患モデルiPS細胞 / 繊毛上皮細胞 / 気道上皮細胞 / 細胞間の繊毛協調運動
Outline of Final Research Achievements

Multiple-ciliated airway epithelial cells have a pivotal role for mucociliary clearance in host defense of the respiratory system and are associated with various airway diseases. It has been challenging to establish co-ordination of airway multiple cilia to generate the unidirectional mucociliary flow in vitro. In the current research, the system of analyzing ciliary function was established based on the comparative analysis between the human iPS cells of healthy donor derived airway multiple-ciliated cells and primary ciliary dyskinesia specific human iPS cells derived airway multiple-ciliated cells. And, the pivotal role of planar cell polarity core protein and apical cytoskelton was indicated by investigating the formative process of coordination of mutiple cilia by using the live cell imaging of primary culture of murine tracheal airway epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

気道上皮細胞シートにおいて一方向性の粘液流を生み出す多繊毛協調運動は、気道を介した生体防御システムの根幹を担うが、多繊毛協調の解析評価システム、並びに多繊毛協調の形成モデルは、確立されていなかった。本研究では、気道上皮細胞シートにおける繊毛機能の解析系を樹立し、多繊毛協調の形成機構に迫った。このことは、今後、粘液繊毛クリアランス異常の気道疾患患者の診断や治療のみならず、これまで評価が難しかった多繊毛協調を軸とした新たな疾患分類に繋がる可能性がある。また、本研究終了時では、論文投稿準備段階であるが、多繊毛協調運動の形成機構の新たなモデルを提示したことは学術的な意義があると考える。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2019 2018

All Journal Article (1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] 肺のオルガノイドとその医学応用への可能性-呼吸器における幹細胞研究の新展開2018

    • Author(s)
      小西 聡史、後藤慎平
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 664-668

    • Related Report
      2018 Annual Research Report
  • [Presentation] High-resolution live-cell imaging analysis toward the formative process of co-ordinated airway ciliary beating(仮)2019

    • Author(s)
      小西 聡史
    • Organizer
      International Conference on Systems Biology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高分解能ライブセルイメージングによる気道多繊毛協調運動構築原理の解明2019

    • Author(s)
      小西 聡史
    • Organizer
      第92回 日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Application of human induced pluripotent stem cells to disease modelling of primary ciliary dyskinesia2019

    • Author(s)
      後藤慎平
    • Organizer
      Gordon Research Conference 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 長時間高分解能ライブセルイメージングによる気管多繊毛上皮細胞の繊毛配列メカニズム の解析2019

    • Author(s)
      月田早智子
    • Organizer
      第11回呼吸機能イメージング研究会学術集会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DISEASE MODELING OF PRIMARY CILIARY DYSKINESIA USING HUMAN INDUCED PLURIPOTENT STEM CELLS2018

    • Author(s)
      曽根 尚之
    • Organizer
      ISSCR Annual Meeting 2018
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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