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Control of differentiation and function of hematopoietic cells by, BCL6 and AP-1 family

BCL6 和 AP-1 家族对造血细胞分化和功能的控制

基本信息

批准号：
18591074
负责人：
OKADA Seiji
金额：
$ 2.48万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591074/
关键词：
BCL6 AP-1 c-Fos Hematopoietic cells Erythroblast Dendritic cells B cells 造血幹細胞

项目摘要

The proto-oncogene bcl-6 and c-fos are ubiquitously expressed in various tissues, and play important role for the differentiation, proliferation, apoptosis and oncogeneisis. In this study, I focused on the function of bcl-6 and c-fos for the hematologic cells, using transgenic and gene deficient mice.1. Function of Bcl-6 on erythroid differentiationBcl-6 detected in the TER119highCD7lhigh subset of erythroblasts in the spleen of neonatal mice may be required to retain the erythroblasts in the cell proliferation stage. In addition, we found that ABCG-2 is also expressed in erythroblast of all of the maturation stage.2. Function of Bcl-6 on dendritic cell differentiationBcl-6 deficient mice showed decreased umber of dendritic cells in spleen. Especially CD8+ subfraction of dendriti cells was completely deficient,.3. Function ofBCL6 on B cell differentiationWe have found that ADAR1 (RNA-editing adenosine deaminase) is one of the target gene of BCL6, and loss of Bc16 cause the higher frequency of somatic hypermultation on B cells.4. Effect of c-Fos ro the regulation of TCRβ recombination.We have found that c-fos directly promotes RAG1/2 binding to the RSS and regulate TCRβ recombination ordering and allelic exclusion.5. Analysis of hematopoietic niche in c-Fos deficient mice.We have found that Magakaryocyte-like cells are appeared in the spleen of c-Fos deficient mice and play an important role in the hematopoietic niche.

原癌基因bcl-6和c-fos广泛表达于各种组织中，在细胞分化、增殖、凋亡和肿瘤发生中起重要作用。本研究以转基因和基因缺陷小鼠为研究对象，研究bcl-6和c-fos基因对血液细胞的作用. Bcl-6在红系分化中的作用新生小鼠脾脏中的成红细胞的TER 119 highCD 7 lhigh亚群中检测到的Bcl-6可能是将成红细胞保持在细胞增殖阶段所必需的。另外，我们发现ABCG-2在所有成熟期的红细胞中也有表达. Bcl-6对树突状细胞分化的影响Bcl-6缺陷小鼠脾脏树突状细胞数量减少。尤其是树突状细胞CD 8+亚群完全缺失。BCL 6在B细胞分化中的作用研究发现，BCL 6的靶基因之一是RNA编辑腺苷脱氨酶1（RNA editing adenosine deaminase，ADAR 1），BCL 16的缺失导致B细胞体细胞超多聚频率增高. c-Fos对TCRβ重组的调控作用研究发现c-Fos直接促进RAG 1/2与RSS的结合，调节TCRβ重组顺序和等位基因排斥. c-Fos基因缺陷小鼠造血生态位的分析我们发现，在c-Fos基因缺陷小鼠的脾脏中出现了巨核细胞样细胞，它们在造血生态位中起着重要作用。