Dynamics of GATA transcription factor expression during erythroid differentiation.
Dynamics of GATA transcription factor expression during erythroid differentiation.
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DOI：
10.1182/blood.v82.4.1071.1071
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发表时间：
1993-08
期刊：
影响因子：
20.3
通讯作者：
M. Leonard;M. Brice;J. D. Engel;T. Papayannopoulou
中科院分区：
文献类型：
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作者：
M. Leonard;M. Brice;J. D. Engel;T. Papayannopoulou
虽然终末分化的红系细胞的形成已经显示需要体内功能性加塔-1基因的存在，但是该转录因子和加塔家族的其他成员在红系细胞分化的早期阶段的作用尚不清楚。在这篇报道中，加塔-1，加塔-2，和加塔-3的表达已经在富集的外周血祖细胞培养之前和之后，在一个良好的特征液体培养系统中进行了检查。此外，分析了原代白血病细胞以及几种红白血病和非红细胞系的加塔因子表达。结果表明，加塔因子在红系细胞中的表达谱与髓系或淋巴系细胞中的表达谱不同。红白血病细胞系表达很少或不表达加塔-3，但表达高水平的加塔-1和加塔-2。当它们被诱导以显示终末红细胞表型时，检测到加塔-1水平的微小变化，但观察到加塔-2水平的显著下降，与细胞达到的成熟程度相称。从外周血富集红系祖细胞导致选择表达加塔-1和加塔-2的细胞。当富集的群体在多种细胞因子存在下悬浮培养时，加塔-1和加塔-2的水平最初增加。然而，在仅含有促红细胞生成素的培养物中，其显示排他的红细胞分化，加塔-1的水平继续增加，而加塔-2表达随着红细胞成熟的进展而下降。相反，缺乏Epo（即，具有白细胞介素-3和kit配体）的培养物显示出向髓系和红系途径的有限进展，并且保持了加塔-1和加塔-2的高水平表达。尽管在后一种培养物中加塔-1表达的初始上调，但在不存在促红细胞生成素的情况下不发生终末红细胞分化。这些结果表明，加塔-1上调与红细胞程序的启动和维持相关，但这两个过程似乎是在单独的监管控制下。因此，在初级红细胞分化过程中发生的不同加塔因子水平的动态变化表明，这些因子的水平可能影响特定造血途径的进展。
Although the formation of terminally differentiated erythroid cells has been shown to require the presence of a functional GATA-1 gene in vivo, the role of this transcription factor and other members of the GATA family at earlier stages of erythroid differentiation is unclear. In this report, the expression of GATA-1, GATA-2, and GATA-3 has been examined in enriched peripheral blood progenitors before and after culture in a well-characterized liquid culture system. In addition primary leukemic cells as well as several erythroleukemic and nonerythroid cell lines were analyzed for GATA factor expression. The results show that the profile of GATA factor expression in erythroid cells is distinct from that of myeloid or lymphoid lineages. Erythroleukemic cell lines express little or no GATA-3, but high levels of GATA-1 and GATA-2. When they are induced to display the terminal erythroid phenotype, little change in the level of GATA-1 is detected but a significant decline in the levels of GATA-2 is observed commensurate with the degree of maturation achieved by the cells. Enrichment of erythroid progenitors from peripheral blood leads to selection of cells that express both GATA-1 and GATA-2. As the enriched populations are cultured in suspension in the presence of multiple cytokines, the levels of both GATA-1 and GATA-2 initially increase. However, in cultures containing only erythropoietin, which show exclusive erythroid differentiation, the levels of GATA-1 continue to increase, whereas GATA-2 expression declines as erythroid maturation progresses. In contrast, cultures lacking Epo (ie, with interleukin-3 and kit ligand) display limited progression towards both the myeloid and erythroid pathways, and high levels of expression of both GATA-1 and GATA-2 are maintained. Despite the initial upregulation of GATA-1 expression in the latter cultures, terminal erythroid differentiation does not occur in the absence of erythropoietin. These results indicate that GATA-1 upregulation is associated with both the initiation and the maintenance of the erythroid program, but that these two processes appear to be under separate regulatory control. Thus, the dynamic changes in the levels of different GATA factors that occur during primary erythroid differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways.