The functional role of FGF signal in the interaction between hypothalamus and pituitary
| Project/Area Number |
18K16232
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kyoto University (2019-2021)
Kobe University (2018) |
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Principal Investigator |
MATSUMOTO Ryusaku 京都大学, iPS細胞研究所, 特別研究員(PD) (20801088)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(6 results)
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[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
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Journal Title
Cell Reports
Volume: 30
Issue: 1
Pages: 18-24
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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