Analysis of expression of transcription factors during erythroid development of hematpoietic stem.

谱系特异性转录因子加塔-1和NF-E2是红细胞生成和巨核细胞生成所必需的。为了阐明造血干细胞向红系分化的机制，我们克隆了NF-E2相关转录因子Nrf 3、BACH 1和BACH 2的cDNA。虽然体内巨核细胞的正常发育需要功能性加塔-1因子的存在，但加塔结合因子的其他成员在巨核细胞分化过程中的作用尚不清楚。在这篇报道中，加塔-1和加塔-2，以及另一个加塔结合因子EVI-1的表达已被检查在富集的脐带血祖细胞培养之前和之后，在一个良好的特点unilineage液体培养系统。在仅含有血小板生成素的培养物中，其显示出排他的巨核细胞分化，加塔-1和加塔-2表达均增加并维持在高水平。相反，在单系红系培养中加塔-2表达下降，尽管加塔-1仍保持在高水平。此外，巨核细胞和红细胞谱系中的EVI-1表达谱与加塔-2的表达谱非常相似。因为Ets结合位点与加塔结合位点存在于所有被描述为对巨核细胞特异性表达重要的区域中，我们还分析了Ets-1表达。很有趣。Ets-1仅在巨核系细胞中被诱导。巨核细胞和红系细胞分化途径彼此密切相关，并且这两种谱系细胞共享许多谱系特异性转录因子。然而，结果表明，这些转录因子在巨核细胞系中的表达谱不同于红系细胞系。在原发性巨核细胞分化过程中发生的加塔结合因子水平的动态变化表明，这些因子的水平可能会影响特定造血途径的进展。

Lineage specific transcription factors, GATA-1 and NF-E2 are essential for erythropoiesis and megakaryocytopoiesis. In order to shed light on the erythroid development of human hematopoietic stem cells, we performed cDNA cloning of novel NF-E2 related transcription factors, Nrf3, BACH1 and BACH2.Although normal megakaryocytic development has been shown to require the presence of a functional GATA-1 factor in vivo, the role of other members of the GATA binding factors during megakaryocytic differentiation is unclear. In this report, the expression of GATA-1 and GATA-2, and another GATA binding factor EVI-1 has been examined in enriched cord blood progenitors before and after culture in a well-characterized unilineage liquid culture system. In the culture containing only thrombopoietin, which show exclusive megakaryocytic differentiation, both GATA-1 and GATA-2 expression was increased and maintained at high levels. In contrast, GATA-2 expression declined in unilineage erythroid culture, although GATA-1 remained at a high level. Furthermore, the profile of EVI-1 expression in megakaryocytic and erythroid lineages was very similar to that of GATA-2. Because Ets binding sites associated with GATA binding sites are present in all regions that have been described as important for megakarycyte-specific expression, we also analyzed Ets-1 expression. Interestingly. Ets-1 was induced only in megakaryocytic lineage cells. Megakaryocytic and erythroid differentiation pathways are closely related to each other, and these two lineage cells share a number of lineage-specific transcription factors. However, the results showed that the profile of the expression of these transcription factors in megakaryocytic cells is distinct from that of erythroid lineage. The dynamic changes in the levels of GATA binding factors that occur during primary megakaryocytic differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways.