Essential and instructive roles of GATA factors in eosinophil development.
GATA transcription factors are major regulators of hematopoietic and immune system. Among GATA factors, GATA-1, GATA-2, and GATA-3 play crucial roles in the development of erythroid cells, hematopoietic stem, and progenitor cells, and T helper type 2 (Th2) cells, respectively. A high level of GATA-1 and GATA-2 expression has been observed in eosinophils, but their roles in eosinophil development remain uncertain both in vitro and in vivo. Here we show that enforced expression of GATA-1 in human primary myeloid progenitor cells completely switches myeloid cell fate into eosinophils. Expression of GATA-1 exclusively promotes development and terminal maturation of eosinophils. Functional domain analyses revealed that the COOH-terminal finger is essential for this capacity while the other domains are dispensable. Importantly, GATA-1-deficient mice failed to develop eosinophil progenitors in the fetal liver. On the other hand, GATA-2 also showed instructive capacity comparable to GATA-1 in vitro and efficiently compensated for GATA-1 deficiency in terms of eosinophil development in vivo, indicating that proper accumulation of GATA factors is critical for eosinophil development. Taken together, our findings establish essential and instructive roles of GATA factors in eosinophil development. GATA-1 and GATA-2 could be novel molecular targets for therapeutic approaches to allergic inflammation.
Hirasawa
Ryutaro
R
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Shimizu
Ritsuko
R
Takahashi
Satoru
S
Osawa
Mitsujiro
M
Takayanagi
Shu
S
Kato
Yuko
Y
Onodera
Masafumi
M
Minegishi
Naoko
N
Yamamoto
Masayuki
M
Fukao
Katashi
K
Taniguchi
Hideki
H
Nakauchi
Hiromitsu
H
Iwama
Atsushi
A
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D009154:Mutation; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D014157:Transcription Factors