【摘要】：造血干細(xì)胞(HSC)自我更新調(diào)控機(jī)制的研究,對(duì)HSC體外修飾和更好地進(jìn)行細(xì)胞治療具有重要的理論意義。本實(shí)驗(yàn)應(yīng)用p18、p27基因敲除小鼠模型研究p18、p27基因缺失對(duì)HSC自我更新的調(diào)控作用及對(duì)造血細(xì)胞植入效率的影響;應(yīng)用逆轉(zhuǎn)錄病毒載體介導(dǎo)HOXB4基因在小鼠造血干、祖細(xì)胞中表達(dá),研究HOXB4對(duì)HSC自我更新的調(diào)控作用及其機(jī)制。研究發(fā)現(xiàn):(1) p18基因缺失可以顯著增強(qiáng)HSC的自我更新能力、顯著提高HSC在亞致死劑量照射小鼠體內(nèi)的長(zhǎng)期植入率;p27基因缺失不能提高HSC在亞致死劑量照射小鼠體內(nèi)的植入率。(3) HOXB4增強(qiáng)HSC的自我更新能力與其促進(jìn)造血細(xì)胞進(jìn)入細(xì)胞周期、增強(qiáng)造血細(xì)胞的增殖能力有關(guān);在基因轉(zhuǎn)錄水平,p18、p21、p27不是HOXB4調(diào)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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R329

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