| Project/Area Number |
26293227
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Honda Hiroaki 広島大学, 原爆放射線医科学研究所, 教授 (40245064)
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| Co-Investigator(Kenkyū-buntansha) |
上田 健 広島大学, 原爆放射線医科学研究所, 助教 (60585149)
本田 善一郎 お茶の水女子大学, 保健管理センター, 教授 (70238814)
稲葉 俊哉 広島大学, 原爆放射線医科学研究所, 教授 (60281292)
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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 |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | ヒストン修飾 / ポリコーム複合体 / EED / コンディショナルノックアウトマウス / 骨髄異形成症候群 / 白血病 / ヒストンメチル化・脱メチル化 / ヒストンH3K27 / PRC2 / JMJD3, UTX / Jmjd3, Utx / ヒストンH3K27メチル化 |
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| Outline of Final Research Achievements |
EED is a component of polycomb repressive complex 2 and is found to be mutated in samples of myelodysplastic syndrome (MDS). We generated conditional heterozygous mice for Eed (Eed+/Δ) and found that Eed+/Δ mice exhibited hematopoietic abnormalities resembling MDS. In addition, in a competitive repopulation assay, Eed+/Δ hematopoietic stem cells (HSCs) showed higher chimerism than control HSCs, and by retrovirus-mediated insertional mutagenesis, Eed+/Δ mice exhibited higher incidence of leukemia than control mice. These results indicate that heterozygosity of Eed induced MDS and rendered high susceptibility to leukemia by enhancing proliferative activity of HSCs.
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