| Project/Area Number |
18K06320
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 44040:Morphology and anatomical structure-related
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 消化管 / 幹細胞 / ニッチ形成 / 甲状腺ホルモン / 変態 / シグナル伝達経路 / アフリカツメガエル / 甲状腺ホルモン受容体 / Hippoシグナル伝達経路 / Foxl1 / 幹細胞ニッチ |
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| Outline of Final Research Achievements |
In the Xenopus laevis intestine, thyroid hormone (TH) induces some of the larval epithelial cells to dedifferentiate into stem cells, around which the niche is formed. In this study, to clarify molecular mechanisms of formation of the stem cell niche, we identified stem cell precursors by using transgenic tadpoles and analyzed their molecular and cellular biological characteristics, focusing on the expression of TH receptors and histone modifications. We also found that fibroblasts expressing Foxl1, which have been recently shown to be essential as niche cells for stem cell maintenance in the adult mammalian intestine, become detectable concomitantly with the appearance of the stem cells in the X. laevis intestine. Furthermore, by using a culture system, we demonstrate that Yap1, a main effector of Hippo signaling, promotes proliferation of both the stem cells and fibroblasts in the X. laevis intestine, suggesting its important role in the stem cell formation.
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| Academic Significance and Societal Importance of the Research Achievements |
変態期に甲状腺ホルモン（TH）により幹細胞が誘導される両生類消化管は、幹細胞の研究に貴重な実験モデルを提供している。本研究ではアフリカツメガエル小腸を使い、哺乳類成体の小腸で上皮再生に重要な役割を果たすHippo経路が、幹細胞ニッチの形成に関わることを初めて報告した。また、哺乳類小腸の主要なニッチ細胞のマーカーであるFoxl1の発現が、THによりShhを介して幹細胞近くの結合組織細胞で誘導されることも見出した。TH依存性のニッチ形成機構は、ヒトに至る陸上脊椎動物共通に保存されていると考えられ、本研究の成果は幹細胞制御に関する理解を深め、再生医療の発展に寄与するものである。
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