Histone modifications in regulating the balance between self-renewal and differentiation of spermatogonia
Project/Area Number |
17K07132
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Laboratory animal science
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Research Institution | The University of Tokyo |
Principal Investigator |
Ozawa Manabu 東京大学, 医科学研究所, 准教授 (80608787)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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Keywords | 精子形成 / 精原細胞 / エピジェネティクス / ヒストン / 制限幹細胞 / 精巣 / 精原幹細胞 / 発生・分化 / 細胞・組織 |
Outline of Final Research Achievements |
Aim of the project is to clarify the function of Fbxl11, a histone demethylase, in spermatogenesis. We have generated and analyzed germ cell-specific Fbxl11 knockout (Fbxl11 cKO) mice. The results showed that Fbxl11 cKO mice were infertile due to marked suppression of spermatogonial differentiation, while self-renew of spermatogonia was not significantly affected. Furthermore, the poor ability for spermatogonial differentiation in Fbxl11 cKO was due to a reduction of mTORC activity in spermatogonia. These results suggest that Fbxl11 regulates spermatogonial differentiation through mTOR signaling.
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Academic Significance and Societal Importance of the Research Achievements |
生殖細胞は次世代に遺伝情報を伝達しうる唯一の細胞系譜であり、その発生を制御する分子基盤を明らかにすることは基礎科学的に極めて興味深い分野であると同時に、不妊・不育が大きな問題となっている今日において社会的にも希求性の高い研究である。本研究では、ヒストン脱メチル化酵素Fbxl11がmTORシグナルを介して精原細胞の分化を調節することを明らかにしており、エピジェネティクス制御を介した精原細胞のホメオスタシス維持機構を理解する上で重要な知見となる。さらに、本研究の成果は新たな不妊治療技術を開発するための一助となることも期待できる。
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility. Science.2020
Author(s)
Kiyozumi D, Noda T, Yamaguchi R, Tobita T, Matsumura T, Shimada K, Kodani M, Kohda T, Fujihara Y, Ozawa M, Yu Z, Miklossy G, Bohren KM, Horie M, Okabe M, Matzuk MM, Ikawa M.
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Journal Title
Science.
Volume: 368
Issue: 6495
Pages: 1132-1135
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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