基因在造血干细胞自我更新中调控作用.docVIP

基因在造血干细胞自我更新中调控作用 　【摘要】 　　造血干细胞( hematopoietic stem cell,HSC) 具有高度自我更新能力和多向分化潜能, HSC 的自我更新是由促进生长的正调控信号和导致凋亡的负调控信号之间的平衡来调控的。在正调控信号中，HOXB4 通过激活不同的信号通路增强HSC 的自我更新，同时又不影响维持正常稳态造血的调控机制。提高HOXB4 的表达水平,能够极大地增强HSC 的自我更新功能，但基本不影响细胞的分化、系特异性及终末细胞的形态和功能。不仅如此，HOXB4 还可增强胚胎干细胞(embryonic stem cell, ESC)的造血潜能，促进ESC 向造血细胞分化。因此，HOXB4和（或）HOXB4 的靶基因的表达上调可能在干细胞移植和基因治疗等方面具有广阔的应用前景。本文就HOXB4基因参与调控造血干细胞的自我更新，HOXB4对HSC的分化特异性及终末分化的“零”效应及HOXB4调控HSC自我更新的分子机制等进行综述。 【关键词】 HOXB4基因 造血干细胞 自我更新 　　Regulatory Role of HOXB4 in Selfrenewal of Hematopoietic Stem Cells ——Review Abstract Selfrenewal and multilineage differentiation of hematopoietic stem cell (HSC) are their functional characteristics. The regulation of HSC selfrenewal is governed by a balance between positive regulatory signals promoting growth and negative regulatory signals resulting in apoptosis. Among the positive regulatory signals, HOXB4 activates distinct pathways that enhance selfrenewal divisions of HSC without overriding the regulatory mechanisms that maintain normal steadystate hemopoiesis. The upregulation of HOXB4 gene expression can greatly promote the HSC selfrenewal, but does not affect the HSC differentiation, the morphology and function of linagespecific cells and terminallydifferentiated blood cells. Furthermore, HOXB4 can enhance the hematopoietic potential of embryonic stem cell (ESC), promoting the differentiation of ESC into hematopoietic cells. As a consequence, upregulation of HOXB4 expression and/or corresponding HOXB4 target genes can have enormous therapeutical potential for human HSC in the stem cell transplantation and gene therapy. In this review the regulatory role of HOXB4 in HSC selfrenewal, “zero” effect of HOXB4 on differentiation specificity of HSC lines and terminal differentiation cells, and molecular mechanisms of regulating HSC selfrenewal by HOXB4 are summarised. Key words HOXB4；hematopoietic stem cell；selfrenewal 造血干细胞(hematopoietic stem cells, HSC)具有高度自我更新能力和多向分化潜能,并能够维持两者之间的平衡。HSC 的自