Regulation of Hemopoietic Stem Cells and Its Clinical Application

我们在三个子项目下开展了这项研究：1)造血干细胞的纯化和扩增，2)造血干细胞的定居、增殖、分化和死亡的信号，3)造血调控因子。我们成功地完成了这项研究。55名参与者成为发行量非常大的期刊的共同作者(影响系数超过20)。129名参与者成为发行量很大的期刊的合著者(影响系数从20到10)。183名参与者成为《血液》的合著者(影响系数，9.745)。205名参与者成为除《血液》以外发行量适中的期刊的联合作者(影响系数从5到10)。得到了以下结果。1)。一种纯化的干细胞拯救了一只受到致命辐射的小鼠。2)。对胚胎干细胞有效分化为血细胞的实验系统进行了改进。3)。调控…的转录因子研究进展促进了更多的血细胞发育。4)剔除了各种缺乏转录因子、造血因子或造血因子受体基因的基因敲除小鼠。5)。信号转导途径从不同的造血因子受体中阐明。JAK-STAT系统在造血因子受体的信号转导中尤为重要。6)。阐述了矮小结构域基因家族的基因敲除小鼠。在基因敲除品系中没有发生肝脏造血，在另一种基因敲除品系中也没有形成骨组织。7)。对c-kit基因功能获得性突变进行研究。肥大细胞瘤由一种突变引起，另一种突变导致可能来自Cajal间质细胞的胃肠道间质瘤。8)。从小鼠早期胚胎中获得的造血干细胞对抑瘤素有反应。β-1蛋白结合Smad3-Smad4复合体，抑制转化生长因子Evi-1受体的信号转导。10)。对细胞凋亡终末阶段的研究取得了显著进展。较少

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