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GATA Motifs Regulate Early Hematopoietic Lineage-Specific Expression of the Gata2 Gene

机译:GATA母题调控Gata2基因的早期造血谱系特异性表达。

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Transcription factor GATA-2 is essential for definitive hematopoiesis, which developmentally emerges from the para-aortic splanchnopleura (P-Sp). The expression of a green fluorescent protein (GFP) reporter placed under the control of a 3.1-kbp Gata2 gene regulatory domain 5′ to the distal first exon (IS) mirrored that of the endogenous Gata2 gene within the P-Sp and yolk sac (YS) blood islands of embryonic day (E) 9.5 murine embryos. The P-Sp- and YS-derived GFP+ fraction of flow-sorted cells dissociated from E9.5 transgenic embryos contained far more CD34+/c-Kit+ cells than the GFP? fraction did. When cultured in vitro, the P-Sp GFP+ cells generated both immature hematopoietic and endothelial cell clusters. Detailed transgenic mouse reporter expression analyses demonstrate that five GATA motifs within the 3.1-kbp Gata2 early hematopoietic regulatory domain (G2-EHRD) were essential for GFP expression within the dorsal aortic wall, where hemangioblasts, the earliest precursors possessing both hematopoietic and vascular developmental potential, are thought to reside. These results thus show that the Gata2 gene IS promoter is regulated by a GATA factor(s) and selectively marks putative hematopoietic/endothelial precursor cells within the P-Sp.
机译:转录因子GATA-2对于确定性造血至关重要,后者从主动脉内脏脾脏(P-Sp)发育而来。置于远端第一个外显子(IS)的3.1 kbp Gata2 基因调控域5'控制下的绿色荧光蛋白(GFP)报告基因的表达与内源性 Gata2的表达相同基因位于9.5天的小鼠胚胎的P-Sp和卵黄囊(YS)血岛中。从E9.5转基因胚胎中解离的流分选细胞的P-Sp-和YS衍生的GFP + 部分包含更多的CD34 + / c-Kit + 细胞比GFP ?分数要好。体外培养时,P-Sp GFP + 细胞会同时生成未成熟的造血细胞和内皮细胞簇。详细的转基因小鼠报道基因表达分析表明,3.1-kbp Gata2 早期造血调节域( G2-EHRD )内的五个GATA基序对于背主动脉壁中GFP的表达至关重要人们认为,成血管细胞是最早的具有成血和血管发育潜能的前体。因此,这些结果表明, Gata2 基因IS启动子受GATA因子调控,并选择性标记P-Sp内的假定造血/内皮前体细胞。

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