造血干细胞(hematopoietic stem cells,HSCs)是典型的成体干细胞,造血系统的稳定依靠造血干细胞正确的自我更新、增殖和分化。TGF-β超家族包括TGF-β、骨生成蛋白(BMP)和激活素,可通过Smad蛋白对造血干细胞进行调节。TGF-β/Smad通路可通过降低CDK4的表达、增加p21蛋白表达和改变p27分布,将造血干细胞阻断于G1期;通过上调CD34表达,抑制造血干细胞的分化。但也有不同的观点,认为TGF-β对HSCs的调节与Smads无关,TGF-β并非通过调控p21和p27抑制HSCs的增殖,TGF-β/Smad通路对维持HSCs静止状态无关。
Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cells,and homeostasis of the hematopoietic system is maintained by their accurate self renewal,proliferation and differentiation. The TGF-β family of ligands,including TGF-β,bone morphogenetic protein (BMP) and activin,signal through Smad pathways to regulate the fate of hematopoietic stem cells. TGF-β/Smad pathway may cause transcriptional activation of CD34 and preserve haematopoietic stem/progenitor cells activity. Also,the pathway may be involved in HSCs' G1 arrest by down-regulating CDK4,up-regulating p21 and redistributing p27. However,there are some conflicting opinions as whether TGF-β regulates HSCs through Smads,whether TGF-β inhibits proliferation of HSCs by p21/p27,and whether the pathway is a control device of HSCs' fate,et al.