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Blood, 15 January 2006, Vol. 107, No. 2, pp. 520-527.
Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-04-1385.
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Submitted April 5, 2005
Accepted September 1, 2005
Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
Jie Zheng, Kenji Kitajima, Eiko Sakai, Tohru Kimura, Naoko Minegishi, Masayuki Yamamoto, and Toru Nakano*
Department of Pathology, Medical School and Frontier Biosciences, Osaka University, Osaka, Japan
Biomedical Engineering Research Organization, Tohoku University, Sendai, Japan
The Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan
* Corresponding author; email: tnakano{at}patho.med.osaka-u.ac.jp.
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 co-culturing 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.
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