| Project/Area Number |
26440184
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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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| Research Field |
Animal physiology/Animal behavior
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| Research Institution | Suntory Foundation for Life Sciences |
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Principal Investigator |
Takahashi Toshio 公益財団法人サントリー生命科学財団, 生物有機科学研究所・統合生体分子機能研究部, 研究員 (20390792)
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| Co-Investigator(Renkei-kenkyūsha) |
YUBA Shunsuke 独立行政法人産業技術総合研究所, 健康工学研究部門, 研究グループ長 (40263248)
SUEMATSU Makoto 慶應義塾大学, 医学部, 教授 (00206385)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 細胞・組織 / シグナル伝達 / 生体分子 / 生理学 / 発生・分化 / 非神経性アセチルコリン / オルガノイド / 腸幹細胞 / コリン作動系 / 腸上皮 / 腸オルガノイド / ニコチン性アセチルコリン受容体 / 腸上皮幹細胞 |
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| Outline of Final Research Achievements |
Non-neuronal acetylcholine (ACh) is predicted to function as a local cell signaling molecule. The physiological significance of the presence of non-neuronal ACh in the intestine remains unclear. Here, experiments using cultured crypt-villus organoids that lack nerve and immune cells led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). Extracts of cultured organoids exhibited a noticeable capacity for ACh synthesis. Treatment of organoids with carbachol down-regulated growth of organoids and expression of marker genes for each epithelial cell type. On the other hand, mAChR antagonists enhanced growth and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from mouse intestinal epithelium maintains the homeostasis of intestinal epithelial cell growth and differentiation via mAChRs.
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