| Project/Area Number |
16H04671
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Hitoshi Seiji 滋賀医科大学, 医学部, 教授 (70300895)
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| Co-Investigator(Kenkyū-buntansha) |
中林 一彦 国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557)
福家 聡 滋賀医科大学, 医学部, 助教 (20422660)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 神経幹細胞 / 神経発生 / エピジェネティクス / ヒストン修飾 / 胚盤胞 / ES細胞 / ヒストンH2B / モノユビキン化 / 未分化性維持 / エピゲノム / ヒストンユビキチン化 / 初期発生 / 運命決定 / モノユビキチン化 / ヒストン / ユビキチン化 / 早期胚 |
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| Outline of Final Research Achievements |
In this study, we analyzed the function of Bre1a, one of epigenetics factors, in the maintenance of neural stem cells. First, we established Bre1a knockout ES cells from embryonic day 3.5 blastocysts of Bre1a-null mice and also generated tetracycline-regulated Bre1a overexpressing ES cells. By examining these ES cell lines, we found that Bre1a-mediated histone H2B monoubiquitylation regulated the expression of many genes, which resulted in the alteration of proliferation and differentiation of ES cells. We further generated Bre1a conditional knockout mice and analyzed the phenotypes of Bre1a-null mouse embryos. We found that Bre1a knockout modified the self-renewal and multipotential capabilities of neural stem cells. We have been investigating the molecular mechanisms underlying these changes.
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| Academic Significance and Societal Importance of the Research Achievements |
脳の発生において極めて重要な役割を果たす神経幹細胞において、様々なエピゲノム修飾因子が織りなすネットワークを解明し、多様な神経細胞・グリア細胞からなる脳が構築される根本原理の一端を明らかにすることができた。
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