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Regulation of Hemopoietic Stem Cells and Its Clinical Application

造血干细胞的调控及其临床应用

基本信息

批准号：
06277103
负责人：
KITAMURA Yukihiko
金额：
$ 65.22万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1998
项目状态：
已结题

项目摘要

We carried out the research under three sub-projects ; 1) purfication and amplification of hemopoietic stem cells, 2) signals for settlement, proliferation, differentiation and death of hemopoietic stem cells, 3) factors for regulation of hemopoiesis. We finished the research with a great success. Fifty five participants became co-authors of very widely circulating journals (impact factor, over 20). One hundred and twenty nine paticipants became co-authors of widely circulating journals (impact factor, 20 to 10). One hundred and eighty three participants became co-authors of Blood (impact factor, 9.745). Two hundred and five participants became co-authors of moderately circulating journals other than Blood (impact factor, 5 to 10). The following results were obtaind. 1). A purified stem cell rescued a lethally irradiated mouse. 2). An experimental system by which embryonic stem cells effiently differentiate to blood cells was improved. 3). Studies of transcription factors that regulate … More development of blood cells were promoted. 4) Various knock-out mice were elabrated that lacked genes encoding transcription factors, hemopoietic factors, or hemopoietic factor receptors. 5). Pathways of signal transduction were clarified from various hemopoietic factor receptors. JAK-STAT systems are especially mportant for the signal transduction from hemopoietic factor receptors. 6). Knock-out mice of runt domain-gene family were elaborated. Liver hemopoiesis did not occur in a knock-out strain, and bone tissue did not develop in the other knock-out strain. 7). Gain-of-function mutations of c-kit gene were studied. Mast cell tumors resulted from one mutation, and gastrointestinal stromal tumors that may be derived from the interstitial cells of Cajal resulted from the other mutation. 8). Hemopoietic stem cells obtained from early mouse embryos responded to oncostatin M. 9). Evi-1 protein bound Smad3-Smad4 complex, and this inhibited the signal transduction from the TGFβ receptor. 10). Studies on the final stage of apoptosis were remarkably progressed. Less

本研究分三个子课题进行：1）造血干细胞的纯化与扩增; 2）造血干细胞的定居、增殖、分化和死亡信号; 3）造血调控因子。我们非常成功地完成了这项研究。55名参与者成为非常广泛发行的期刊的共同作者（影响因子，超过20）。129名患者成为广泛流通期刊的共同作者（影响因子，20至10）。183名参与者成为《血液》的合著者（影响因子，9.745）。205名参与者成为中等流通期刊的共同作者，而不是血液（影响因子，5至10）。获得了以下结果。1）。一个纯化的干细胞拯救了一只受到致命辐射的老鼠。2）。改进了胚胎干细胞高效分化为血细胞的实验体系。3）。转录因子的研究 ...更多信息促进了血细胞的发育。4)各种基因敲除小鼠被鉴定为缺乏编码转录因子、造血因子或造血因子受体的基因。5）。从各种造血因子受体阐明了信号转导途径。JAK-STAT系统在造血因子受体的信号转导中起着重要作用。6）。阐述了runt结构域基因家族的基因敲除小鼠。肝造血没有发生在一个敲除菌株，和骨组织没有开发的其他敲除菌株。7）。研究c-kit基因的功能获得性突变。肥大细胞瘤由一种突变引起，而可能源自Cajal间质细胞的胃肠道间质瘤由另一种突变引起。8）。从早期小鼠胚胎中获得的造血干细胞对制瘤素M有反应。9）。Evi-1蛋白与Smad 3-Smad 4复合物结合，抑制TGFβ受体的信号转导。10）。细胞凋亡终末期的研究取得了显著进展。少