Hematopoietic stem cell maintenance by Mediator transcriptional coregulator complex

介体转录共调节复合物维持造血干细胞

• 批准号: 23591388
• 负责人: ITO Mitsuhiro
• 金额: $ 3.33万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591388/
• 关键词: FGF7; hematopoietic niche; stromal cells; MED1; Mediator; メディエーター転写複合体; 造血ニッチ; 骨髄芽球性白血病; 転写メディエーター; RNAポリメラーゼII; オステオポンチン; CD44

FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1-/- MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in wild type MEFs, MED1 knockout MEFs, and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

在缺乏介体转录辅助调节复合体MED1亚单位的小鼠胚胎成纤维细胞(MEF)中，FGF7的表达减弱。当正常小鼠骨髓(BM)细胞与BM基质细胞在抗Fgf7抗体存在下共同培养时，BM细胞的生长和长时间培养启动细胞(LTC-ICs)的数量显著减少。抗Fgf7抗体还可抑制MB1基质细胞依赖的髓母细胞瘤细胞的增殖和鹅卵石形成。在BM细胞与MED_1-/-MEF共培养中加入重组Fgf7可增加BM细胞和LTC-IC的数量。BM细胞表达FGFF7及其同源受体FGFR2IIIb，而MEF和BM基质细胞均表达FGFF7和FGFR2IIIb。FGF7激活野生型MEF、MED1基因敲除型MEF和骨髓基质细胞中FGFR2IIIb的下游靶点。综上所述，我们认为Fgf7通过表达在基质细胞上的FGFR2IIIb间接支持HSPC和白血病启动细胞。

项目成果

CoCoA/CCAR1 pair-mediated recruitment of Mediator complex indicates novel pathway for the function of GATA1 in erythroid differentiation

CoCoA/CCAR1 对介导的介导复合物的募集表明 GATA1 在红系分化中发挥作用的新途径

• 发表时间: 2011
• 作者: C. Kaminaga;S. Mizuta;T. Minami;K. Oda;H. Fujita;K. Matsui;R. Ishino;Sumitomo;N. Urahama;M. Ito
• 通讯作者: M. Ito

血液疾患と発熱

血液疾病和发烧

• 发表时间: 2013
• 作者: Uozumi K;Ishida T;T jo T;Suzushima H;Takemoto S;Yamamoto K;Uike N;Saburi Y;Nosaka K;Utsunomiya A;Tobinai K;fujiwara H;Ishituka K;Yoshida Y;Taira N;Moriuchi U,I mada K;Miyamot T;Tsukasaki K;Tomonaga M;Ueda R;伊藤光宏
• 通讯作者: 伊藤光宏

FGF7 supports mouse hematopoietic stem and progenitor cells via FGFR2IIIb expressed on stromal cells.

FGF7 通过基质细胞上表达的 FGFR2IIIb 支持小鼠造血干细胞和祖细胞。

• 发表时间: 2013
• 作者: Ruri Ishino;Kaori Minami;Yukiko Ikeuchi;Masaya Yano;Azusa Imanishi;Satowa Tanaka;Kenji Yonezawa;Keiji Matsui;Shumpei Mizuta;Shigetaka Asano;Mitsuhiro Ito
• 通讯作者: Mitsuhiro Ito

Self-Organized Criticality Theory and the Expansion of PD-1-Positive Effector CD4 T Cells: Search for Autoantibody-Inducing CD4 T Cells.

• DOI: 10.3389/fimmu.2013.00087
• 发表时间: 2013
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Miyazaki Y;Tsumiyama K;Yamane T;Ito M;Shiozawa S
• 通讯作者: Shiozawa S

CCAR1/CoCoA-mediated Mediator recruitment indicates novel pathway for GATA1 action in erythropoiesis.

CCAR1/CoCoA 介导的介质招募表明 GATA1 在红细胞生成中发挥作用的新途径。

• 发表时间: 2012
• 作者: Shumpei Mizuta;Chihiro Kaminaga;Haruka Fujita;Keiji Matsui;Ruri Ishino;Kasumi Oda;Azusa Fujita;Nana Kubota;Norinaga Urahama;Mitsuhiro Ito
• 通讯作者: Mitsuhiro Ito