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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...

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Autores principales: Hirasawa, Ryutaro, Shimizu, Ritsuko, Takahashi, Satoru, Osawa, Mitsujiro, Takayanagi, Shu, Kato, Yuko, Onodera, Masafumi, Minegishi, Naoko, Yamamoto, Masayuki, Fukao, Katashi, Taniguchi, Hideki, Nakauchi, Hiromitsu, Iwama, Atsushi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193540/
https://www.ncbi.nlm.nih.gov/pubmed/12045236
http://dx.doi.org/10.1084/jem.20020170
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author Hirasawa, Ryutaro
Shimizu, Ritsuko
Takahashi, Satoru
Osawa, Mitsujiro
Takayanagi, Shu
Kato, Yuko
Onodera, Masafumi
Minegishi, Naoko
Yamamoto, Masayuki
Fukao, Katashi
Taniguchi, Hideki
Nakauchi, Hiromitsu
Iwama, Atsushi
author_facet Hirasawa, Ryutaro
Shimizu, Ritsuko
Takahashi, Satoru
Osawa, Mitsujiro
Takayanagi, Shu
Kato, Yuko
Onodera, Masafumi
Minegishi, Naoko
Yamamoto, Masayuki
Fukao, Katashi
Taniguchi, Hideki
Nakauchi, Hiromitsu
Iwama, Atsushi
author_sort Hirasawa, Ryutaro
collection PubMed
description 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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spelling pubmed-21935402008-04-14 Essential and Instructive Roles of GATA Factors in Eosinophil Development Hirasawa, Ryutaro Shimizu, Ritsuko Takahashi, Satoru Osawa, Mitsujiro Takayanagi, Shu Kato, Yuko Onodera, Masafumi Minegishi, Naoko Yamamoto, Masayuki Fukao, Katashi Taniguchi, Hideki Nakauchi, Hiromitsu Iwama, Atsushi J Exp Med Article 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. The Rockefeller University Press 2002-06-03 /pmc/articles/PMC2193540/ /pubmed/12045236 http://dx.doi.org/10.1084/jem.20020170 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Hirasawa, Ryutaro
Shimizu, Ritsuko
Takahashi, Satoru
Osawa, Mitsujiro
Takayanagi, Shu
Kato, Yuko
Onodera, Masafumi
Minegishi, Naoko
Yamamoto, Masayuki
Fukao, Katashi
Taniguchi, Hideki
Nakauchi, Hiromitsu
Iwama, Atsushi
Essential and Instructive Roles of GATA Factors in Eosinophil Development
title Essential and Instructive Roles of GATA Factors in Eosinophil Development
title_full Essential and Instructive Roles of GATA Factors in Eosinophil Development
title_fullStr Essential and Instructive Roles of GATA Factors in Eosinophil Development
title_full_unstemmed Essential and Instructive Roles of GATA Factors in Eosinophil Development
title_short Essential and Instructive Roles of GATA Factors in Eosinophil Development
title_sort essential and instructive roles of gata factors in eosinophil development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193540/
https://www.ncbi.nlm.nih.gov/pubmed/12045236
http://dx.doi.org/10.1084/jem.20020170
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