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.
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3 June 2002
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June 03 2002
Essential and Instructive Roles of GATA Factors in Eosinophil Development
Ryutaro Hirasawa,
Ryutaro Hirasawa
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
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Ritsuko Shimizu,
Ritsuko Shimizu
2Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences
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Satoru Takahashi,
Satoru Takahashi
3Department of Anatomy and Embryology, Institute of Basic Medical Sciences
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Mitsujiro Osawa,
Mitsujiro Osawa
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
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Shu Takayanagi,
Shu Takayanagi
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
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Yuko Kato,
Yuko Kato
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
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Masafumi Onodera,
Masafumi Onodera
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
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Naoko Minegishi,
Naoko Minegishi
4College of Medical Technology and Nursing, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
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Masayuki Yamamoto,
Masayuki Yamamoto
2Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences
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Katashi Fukao,
Katashi Fukao
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
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Hideki Taniguchi,
Hideki Taniguchi
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
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Hiromitsu Nakauchi,
Hiromitsu Nakauchi
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
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Atsushi Iwama
Atsushi Iwama
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
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Ryutaro Hirasawa
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Ritsuko Shimizu
2Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences
Satoru Takahashi
3Department of Anatomy and Embryology, Institute of Basic Medical Sciences
Mitsujiro Osawa
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Shu Takayanagi
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
Yuko Kato
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
Masafumi Onodera
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
Naoko Minegishi
4College of Medical Technology and Nursing, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Masayuki Yamamoto
2Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences
Katashi Fukao
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Hideki Taniguchi
5Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Hiromitsu Nakauchi
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Atsushi Iwama
1Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Address correspondence to Atsushi Iwama and Hiromitsu Nakauchi, Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Phone: 81-3-5449-5332; Fax: 81-3-5449-5451; E-mail: [email protected] or [email protected]
*
Abbreviations used in this paper: C/EBP, CCAAT/enhancer binding protein; EGFP, enhanced GFP; EPO, eosinophil peroxidase; FOG-1, friend of GATA-1; GFP, green fluorescent protein; MBP, major basic protein; RT, reverse transcription.
Received:
February 01 2002
Revision Received:
April 12 2002
Accepted:
April 15 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (11): 1379–1386.
Article history
Received:
February 01 2002
Revision Received:
April 12 2002
Accepted:
April 15 2002
Citation
Ryutaro Hirasawa, Ritsuko Shimizu, Satoru Takahashi, Mitsujiro Osawa, Shu Takayanagi, Yuko Kato, Masafumi Onodera, Naoko Minegishi, Masayuki Yamamoto, Katashi Fukao, Hideki Taniguchi, Hiromitsu Nakauchi, Atsushi Iwama; Essential and Instructive Roles of GATA Factors in Eosinophil Development . J Exp Med 3 June 2002; 195 (11): 1379–1386. doi: https://doi.org/10.1084/jem.20020170
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