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作 者:李滨[1] 胡诗帆 孙园园[1] 郭驰[1] 张健[1] 杨寅柯[1]
出 处:《生命科学研究》2016年第4期283-289,共7页Life Science Research
基 金:"985工程"专项资金资助项目(531109020011)
摘 要:GATA-2作为GATA家族成员,其通过与靶基因的GATA结合位点结合,在造血系统发育中起关键性的调节作用。VentX是非洲爪蟾蜍xvent基因同源的哺乳动物基因,最近研究发现,其参与了中胚层的分化定型及造血干细胞的维持,并且在细胞衰老、增殖、分化及炎症反应等的调节中发挥功能。为探索VentX基因与GATA-2的关系及其对造血干细胞红系分化的调节功能,首先在K562细胞株中进行了VentX启动子分析,发现GATA-2可以通过结合到VentX启动子区两个GATA结合位点来顺式调控Vent X;继而在人骨髓(造血)干细胞中的实验显示,过表达GATA-2或过表达VentX,均可抑制CD34^+细胞的增殖,促进CD34^+细胞向红系分化。以上实验结果为临床红细胞来源提供了有价值的研究线索。GATA-2, a member of the GATA-motif-binding family, plays key roles in hematopoietic develop- ment, functions by occupying GATA-binding sites of target genes. According to recent studies, the VentX gene, a mammalian homolog of the Xenopus xvent gene, is involved in mesodermal patterning and hematopoietic stem cells maintenance, and has regulatory roles in cellular senescence, proliferation, differentiation, and inflammation. To explore the relationship between VentX gene and GATA-2 and the regulatory functions of VentX in hematopoietic stem cells undergoing erythroid differentiation, promoter analysis of VentX in K562 cells was conducted and the results showed that GATA-2 can bind with two cis-regulatory elements of VentX promoter. Subsequently, the data were showed that overexpression of GA TA-2 or VentX inhibited CD34+cell proliferation in human bone marrow (hematopoietic) stem cells and induced erythroid differentiation of CD34+ cells. It provides us with a valuable clue for the source of red blood cells in clinic.
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