Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells

• Published in: Blood 2006-01, Vol.107 (2), p.520-527
• Main Authors: Zheng, Jie, Kitajima, Kenji, Sakai, Eiko, Kimura, Tohru, Minegishi, Naoko, Yamamoto, Masayuki, Nakano, Toru
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Biological and medical sciences; Blood coagulation. Blood cells; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Coculture Techniques; Erythroid Cells - cytology; Erythroid Cells - drug effects; Erythroid Cells - metabolism; Erythropoiesis - physiology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; GATA1 Transcription Factor - pharmacology; Gene Expression Regulation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Homozygote; Humans; Molecular and cellular biology; Mutation; Platelet; Retroviridae - genetics; Stromal Cells - cytology; Stromal Cells - drug effects; Stromal Cells - metabolism; Tetracycline - pharmacology; Transcriptional Activation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-04-1385

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.