Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
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DOI：
10.1182/blood-2005-04-1385
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发表时间：
2006-01-15
期刊：
影响因子：
20.3
通讯作者：
Nakano, T
中科院分区：
文献类型：
--
作者：
Zheng, J;Kitajima, K;Nakano, T
锌指转录因子加塔-1对原始（胚胎）和定形（成人）红细胞生成都是必需的。为了确定加塔-1在原始和定形红细胞的产生和分化中的作用，我们建立了加塔-1缺失的胚胎干细胞系，其中加塔-1能够通过使用四环素条件基因表达系统进行条件表达。通过在0 P9基质细胞上共培养使细胞经历造血分化。我们在原始和定型红细胞生成过程中表达加塔-1，并分析了加塔-1拯救由加塔-1无效突变引起的红细胞生成缺陷的能力。我们的研究结果表明，加塔-1功能的增殖和成熟的红细胞在一个独特的方式。加塔-1在原始和定型红细胞生成过程中的早期表达足以促进红细胞的增殖。相反，加塔-1的晚期表达对于原始红细胞和定形红细胞的终末分化是必不可少的。因此，加塔-1通过不同的机制影响红细胞的增殖和分化。
The zinc finger transcription factor GATA-1 is essential for both primitive (embryonic) and definitive (adult) erythropoiesis. To define the roles of GATA-1 in the production and differentiation of primitive and definitive erythrocytes, we established GATA-1-null embryonic stem cell lines in which GATA-1 was able to be conditionally expressed by using the tetracycline conditional gene expression system. The cells were subjected to hematopoietic differentiation by coculturing on OP9 stroma cells. We expressed GATA-1 in the course of primitive and definitive erythropoiesis and analyzed the ability of GATA-1 to rescue the defective erythropoiesis caused by the GATA-1 null mutation. Our results show that GATA-1 functions in the proliferation and maturation of erythrocytes in a distinctive manner. The early-stage expression of GATA-1 during both primitive and definitive erythropoiesis was sufficient to promote the proliferation of red blood cells. In contrast, the late-stage expression of GATA-1 was indispensable to the terminal differentiation of primitive and definitive erythrocytes. Thus, GATA-1 affects the proliferation and differentiation of erythrocytes by different mechanisms.