JMJD3 plays essential roles in the maintenance of hematopoietic stem cells and leukemic stem cells.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18418
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Hiroshima University
• Principal Investigator: Yamasaki Norimasa 広島大学, 技術センター, 技術主任 (70564136)
• Project Period (FY): 2016-04-01 – 2018-03-31
• 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

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.

Free Research Field

分子細胞生物学