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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Pre-mRNA-splicing factor SF3B1 regulates repopulating capacity of hematopoietic stem cells

演題番号 : OS-1-94

王 長山 (Changshan Wang):1,2、指田 吾郎 (Goro Sashida):1,2、古関 明彦 (Haruhiko Koseki):3、岩間 厚志 (Atsushi Iwama):1,2

1:Cellular and Molecular Medicine,Chiba Univ.,Japan、2:JST, CREST, Tokyo, Japan、3:RIKEN Research Center for Allergy and Immunology, Yokohama, Japan

 

Alternative pre-mRNA splicing is a key process of biological diversity and the normal gene expression. Mis-regulation of normal splicing patterns may give rise to pathophysiological processes and has been associated with modify human diseases. Numerous studies in recent years have reported that mutations involving multiple components of the mRNA splicing machinery including SF3B1 in patients with MDS. Furthermore, one of the most frequently mutated spliceosome component SF3B1 was mutated in 70-85% of RARS cases and is highly associated with the presence of ringed sideroblasts. Here, we identify an evolutionarily conserved SF3B1 regulate HSC proliferation and differentiation. While the Sf3b1 homozygous knockout mice die during embryonic development around the 16 to 32cell stage, and heterozygous mice are born healthy. In the noncompetitive bone marrow reconstitution assays, BM cells from SF3b1+/- showed no obvious defects in reconstituting hematopoiesis of recipient mice and induced no hematological malignancies within a year. In contrast, in the competitive reconstitution assays, SF3b1+/- BM cells showed modest but significant impairment in repopulating capacity. Nonetheless, SF3b1+/- BM cells did not show obvious defects in differentiation. Next we knocked down SF3b1 in SF3b1+/-HSCs .We found that depletion of Sf3b1 to the levels around 1/4 of that in wild type cells causes marked inhibition of cell growth both in vitro and in vivo. Accordingly, these findings suggest that the level of Sf3b1 gene expression is critical in the maintenance of self-renewal capacity of HSCs.

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