Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors.
Transcription factor GATA-1 plays an important role in gene regulation during the development of erythroid cells. Several reports suggest that GATA-1 plays multiple roles in survival, proliferation, and differentiation of erythroid cells. However, little is known about the relationship between the level of GATA-1 expression and its nature of multifunction to affect erythroid cell fate. To address this issue, we developed in vitro embryonic stem (ES) culture system by using OP9 stromal cells (OP9/ES cell co-culture system), and cultured the mutant (GATA-1.05 and GATA-1-null) and wild type (WT)ES cells, respectively. By using this OP9/ES cell co-culture system, primitive and definitive erythroid cells were developed individually, and we examined how expression level of GATA-1 affects the development of erythroid cells. GATA-1.05 ES-derived definitive erythroid cells were immature with the appearance of proerythroblasts, and highly proliferated, compared with WT and GATA-1-null ES-derived erythroid cells. Extensive studies of cell cycle kinetics revealed that the GATA-1.05 proerythroblasts accumulated in S phase and expressed lower levels of p16(INK4A) than WT ES cell-derived proerythroblasts. We concluded that GATA-1 must achieve a critical threshold activity to achieve selective activation of specific target genes, thereby influencing the developmental decision of an erythroid progenitor cell to undergo apoptosis, proliferation, or terminal differentiation.
Pan
Xiaoqing
X
Department of Molecular and Developmental Biology, Center for TARA, ERATO Environmental Response Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
Ohneda
Osamu
O
Ohneda
Kinuko
K
Lindeboom
Fokke
F
Iwata
Fumiko
F
Shimizu
Ritsuko
R
Nagano
Masumi
M
Suwabe
Naruyoshi
N
Philipsen
Sjaak
S
Lim
Kim-Chew
KC
Engel
James D
JD
Yamamoto
Masayuki
M
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism; D015672:Erythroid Precursor Cells; D050981:Erythroid-Specific DNA-Binding Factors; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor; D005822:Genetic Vectors; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D012190:Retroviridae / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry
D019941:Cyclin-Dependent Kinase Inhibitor p16; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors