细胞周期素依赖激酶抑制因子在造血干细胞自我更新调控中的作用

发布时间：2018-09-01 08:35

【摘要】：造血干细胞(HSC)自我更新调控机制的研究,对HSC体外修饰和更好地进行细胞治疗具有重要的理论意义。本实验应用p18、p27基因敲除小鼠模型研究p18、p27基因缺失对HSC自我更新的调控作用及对造血细胞植入效率的影响;应用逆转录病毒载体介导HOXB4基因在小鼠造血干、祖细胞中表达,研究HOXB4对HSC自我更新的调控作用及其机制。研究发现:(1) p18基因缺失可以显著增强HSC的自我更新能力、显著提高HSC在亚致死剂量照射小鼠体内的长期植入率;p27基因缺失不能提高HSC在亚致死剂量照射小鼠体内的植入率。(3) HOXB4增强HSC的自我更新能力与其促进造血细胞进入细胞周期、增强造血细胞的增殖能力有关;在基因转录水平,p18、p21、p27不是HOXB4调控HSC自我更新的下游因子。
[Abstract]:The study on the mechanism of self-renewal of hematopoietic stem cells (HSC) has important theoretical significance for HSC modification in vitro and better cell therapy. In this study, we used p18 p27 knockout mouse model to study the effect of p18 p27 gene deletion on self-renewal of HSC and its effect on hematopoietic cell implantation efficiency, and the expression of HOXB4 gene in hematopoietic stem and progenitor cells of mice was mediated by retrovirus vector. To study the regulatory effect of HOXB4 on HSC self-renewal and its mechanism. The results showed that: (1) the deletion of p18 gene could significantly enhance the self-renewal ability of HSC. The deletion of p27 gene did not increase the implantation rate of HSC in sublethal dose irradiated mice. (3) HOXB4 enhanced the self-renewal ability of HSC and promoted hematopoietic cells to enter cell cycle. The enhancement of hematopoietic cell proliferation is related to the increase of hematopoietic cell proliferation, and p18p21, p27 is not a downstream factor of HOXB4 regulating HSC self-renewal at the gene transcription level.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R329

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