Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos.
The aorta-gonads-mesonephros (AGM) region of the mouse embryo has been assigned as the origin of definitive hematopoiesis. The transcription factor GATA-2 has specific but unclarified roles in early hematopoiesis. To elucidate the expression profile of GATA-2, we prepared transgenic mouse lines containing the green fluorescent protein (GFP) gene driven by GATA-2 gene regulatory elements. We also prepared a mouse line in which GFP reporter sequences were inserted into the endogenous GATA-2 gene. Both mouse mutants expressed GFP in the early hematopoietic tissues. The CD45 antigen, a marker of hematopoietic cells, was expressed in a small fraction of transgene (TG)-derived GFP+ cells. The remaining TG-GFP+/CD45- cells were adherent to plastic and produced CD45+ hematopoietic cells abundantly when cultured in vitro. Exogenous expression of GATA-2 in TG-GFP+/CD45- cells from the AGM region inhibited their differentiation into CD45+ cells. Loss of GATA-2 function through the disruption of the GATA-2 locus enhanced the earlier emergence of CD45+ cells in the yolk sac of the 9.5-day conceptus. These results demonstrated that GATA-2 is expressed in the precursor of hematopoietic cells and works as a gatekeeper to preserve their immaturity. A reduction of GATA-2 expression or activity is required for the differentiation of precursors to hematopoietic cells.
Minegishi
Naoko
N
Institute of Basic Medical Sciences, Tsukuba, Japan.
Suzuki
Norio
N
Yokomizo
Tomomasa
T
Pan
Xiaoqing
X
Fujimoto
Tetsuhiro
T
Takahashi
Satoru
S
Hara
Takahiko
T
Miyajima
Atsushi
A
Nishikawa
Shin-Ichi
S
Yamamoto
Masayuki
M
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology*; D050989:GATA2 Transcription Factor; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; D008164:Luminescent Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens