Regulation of Hemopoietic Stem Cells and Its Clinical Application

我们在三个子项目下进行了研究；1)造血干细胞的纯化和扩增；2)造血干细胞的定居、增殖、分化和死亡信号；3)造血调节因子。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流通的期刊的共同作者（影响因子，超过20）。129名参与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Blood的共同作者（影响因子，9.745）。225名参与者成为《血液》以外的中等发行量期刊的合著者（影响因子，5到10）。得到了以下结果：1）. 一个纯化的干细胞拯救了一只受到致命辐射的老鼠。2)。改进了胚胎干细胞向血细胞有效分化的实验系统。3)。对调节…的转录因子的研究促进了更多血细胞的发育。4)阐明了多种缺失编码转录因子、造血因子或造血因子受体基因的敲除小鼠。5)。阐明了各种造血因子受体的信号转导途径。JAK-STAT系统对造血因子受体的信号转导尤为重要。6)。对矮子结构域基因家族敲除小鼠进行了阐述。在一种基因敲除菌株中没有发生肝脏造血，而在另一种基因敲除菌株中没有形成骨组织。7)。研究了c-kit基因的功能获得突变。肥大细胞瘤是由一种突变引起的，而胃肠道间质瘤可能来源于Cajal间质细胞，是由另一种突变引起的。8)。从早期小鼠胚胎中获得的造血干细胞对肿瘤抑制素有反应(9)。Evi-1蛋白结合Smad3-Smad4复合物，这抑制了TGFβ受体的信号转导。10)。对细胞凋亡最后阶段的研究进展显著。少

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