Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells.
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.
Zheng
Jie
J
Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan.
Kitajima
Kenji
K
Sakai
Eiko
E
Kimura
Tohru
T
Minegishi
Naoko
N
Yamamoto
Masayuki
M
Nakano
Toru
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D009154:Mutation; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D015533:Transcriptional Activation
D000900:Anti-Bacterial Agents; D050982:GATA1 Transcription Factor; D013752:Tetracycline