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The functional role of FGF signal in the interaction between hypothalamus and pituitary

Research Project

Project/Area Number 18K16232
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKyoto University (2019-2021)
Kobe University (2018)

Principal Investigator

MATSUMOTO Ryusaku  京都大学, iPS細胞研究所, 特別研究員(PD) (20801088)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords下垂体 / 視床下部 / 線維芽細胞増殖因子 (FGF) / 口腔外胚葉 / iPS細胞 / 下垂体発生 / FGF / 線維芽細胞増殖因子 / FGFシグナル / 発生学
Outline of Final Research Achievements

We have investigated the role of hypothalamic FGF signals in pituitary development using iPSC-based hypothalamus-pituitary organoid. Knockout of FGF in iPSCs demonstrated that FGF8 was important for survival of oral ectoderm cells and FGF10 regulated LHX3+ pituitary progenitor cell differentiation. Treatment of FGFR inhibitor experiments showed that hypothalamic FGF signals have essential role in maintenance of oral ectoderm cells but no significant effect on pituitary hormone-producing cell differentiation. Interestingly, in later stage of differentiation, FGF signals are important for functional maturation of pituitary hormone-producing cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトiPS細胞の分化誘導系を用いることで、これまで解析が困難であったヒトの下垂体発生をin vitroで再現し経時的に解析可能であることを示した。それによって、視床下部に発現するFGFシグナルが下垂体発生にどのように関わっており、それが実際に下垂体疾患の発症に関わっていることを示すことができた。本モデルはヒトの下垂体発生・疾患モデルとして非常に有用であり、今後更なるヒト発生学の知見を生み出すとともに、ヒト下垂体疾患における病態の解明や治療法の開発に資するものとして大いに期待される。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Human pituitary development and application of iPSCs for pituitary disease2020

    • Author(s)
      Matsumoto Ryusaku、Takahashi Yutaka
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 78 Issue: 5 Pages: 2069-2079

    • DOI

      10.1007/s00018-020-03692-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells.2020

    • Author(s)
      Kasai T, Suga H, Sakakibara M, Ozone C, Matsumoto R, Kano M, Mitsumoto K, Ogawa K, Kodani Y, Nagasaki H, Inoshita N, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Iwama S, Goto M, Banno R, Takahashi J, Arima H
    • Journal Title

      Cell Reports

      Volume: 30 Issue: 1 Pages: 18-24

    • DOI

      10.1016/j.celrep.2019.12.009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells2019

    • Author(s)
      Matsumoto Ryusaku、Suga Hidetaka、Aoi Takashi、Bando Hironori、Fukuoka Hidenori、Iguchi Genzo、Narumi Satoshi、Hasegawa Tomonobu、Muguruma Keiko、Ogawa Wataru、Takahashi Yutaka
    • Journal Title

      Journal of Clinical Investigation

      Volume: 130 Issue: 2 Pages: 641-654

    • DOI

      10.1172/jci127378

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Spatial Transcriptomics for the Analysis of Human Pituitary Development2021

    • Author(s)
      Ryusaku Matsumoto、Mio Kabata、Hidetaka Suga、Takuya Yamamoto
    • Organizer
      ENDO 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 下垂体発生における視床下部-口腔外胚葉間FGFの役割2019

    • Author(s)
      松本隆作, 青井貴之, 小柳三千代, 須賀英隆, 福岡秀規, 井口元三, 小川渉, 高橋裕
    • Organizer
      第92回内分泌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 下垂体発生における視床下部-口腔外胚葉間FGFの役割2019

    • Author(s)
      松本 隆作、青井 貴之、小柳 三千代、須賀 英隆、福岡 秀規、井口 元三、小川 渉、高橋 裕
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-12-25  

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