演題詳細

一般口演 / Oral Session

一般口演 18 (Oral Session 18) :エピジェネティクス

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
瀧原 義宏 (Yoshihiro Takihara):1
1:広島大学原爆放射線医科学研究所 幹細胞機能学研究分野
 
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EED, a subunit of PRC2, plays an essential role in maintenance of adult hematopoietic stem cells

演題番号 : OS-1-90

池田 健一郎 (Ken-Ichiro Ikeda):1、上田 健 (Takeshi Ueda):1、長町 安希子 (Akiko Nagamachi):2、山崎 憲政 (Norimasa Yamasaki):1、中田 雄一郎 (Yuichiro Nakata):1、稲葉 俊哉 (Toshiya Inaba):2、本田 浩章 (Hiroaki Honda):1

1:Dept. Disease Model, Inst. Rad. Biol. Med., Hiroshima Univ., Japan、2:Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan

 

EED (embryonic ectoderm development) is a non-catalytic component of polycomb repressive complex 2 (PRC2) that propagates trimethylated H3K27 (H3K27me3) and mediates transcription repression. We previously identified functionally defective EED mutations (exon deletions and missense mutations) in patients with myelodysplastic syndrome and related diseases. This suggests that EED is required for normal hematopoiesis in human adults, but its precise role remains unclear. To address this issue, we generated and analyzed Eed conditional knockout (cKO) mice. Acquired deletion of EED resulted in lethality in adult mice. The thymus and spleen were atrophic, and cell numbers of all hematopoietic lineages were markedly reduced with a prominent decrease of c-kit-positive cells. Also, global H3K27me3 levels were significantly reduced in the hematopoietic tissues. These results demonstrate that EED plays an essential role in the maintenance of hematopoietic homeostasis by regulating H3K27me3. The molecular mechanism(s) by which EED regulates hematopoietic stem cells is currently investigated. In addition, we are searching whether EED haploinsufficiency leads to leukemia susceptibility using Eed cKO heterozygotes infected with replication-competent retroviruses.

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