| Project/Area Number |
16K18418
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | JMJD3 / 造血幹細胞 / 白血病 / エピジェネティクス / ノックアウトマウス / ヒストン脱メチル化酵素 / Jmjd3(Kdm6b) / コンディショナルノックアウトマウス / Jmjd3 |
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| Outline of Final Research Achievements |
JMJD3 (Jumonji domain-containing 3) is a demethylase for histone H3 at Lys27 (H3K27) and contributes to various cellular processes including senescence, proliferation and differentiation. However, the roles of JMJD3 in normal hematopoiesis and leukemogenesis remain largely unknown. To address this issue, we generated conditional KO (cKO) mice for Jmjd3. Jmjd3-deficient mice did not show obvious hematopoietic abnormalities at steady state. However, under stress conditions, such as replicative stress by serial bone marrow transplantation and oncogenic stress by MLL-AF9-induced leukemia, Jmjd3-deficient hematopoietic stem and progenitor cells exhibited significant defects in the maintenance of stem cell activity. Cell cycle and gene set enrichment analyses revealed that Jmjd3-deficient HSCs exhibited excessive proliferation and loss of quiescence.
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