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GATA-3 is required for early T lineage progenitor development

Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation...

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Autores principales: Hosoya, Tomonori, Kuroha, Takashi, Moriguchi, Takashi, Cummings, Dustin, Maillard, Ivan, Lim, Kim-Chew, Engel, James Douglas
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806453/
https://www.ncbi.nlm.nih.gov/pubmed/19934022
http://dx.doi.org/10.1084/jem.20090934
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author Hosoya, Tomonori
Kuroha, Takashi
Moriguchi, Takashi
Cummings, Dustin
Maillard, Ivan
Lim, Kim-Chew
Engel, James Douglas
author_facet Hosoya, Tomonori
Kuroha, Takashi
Moriguchi, Takashi
Cummings, Dustin
Maillard, Ivan
Lim, Kim-Chew
Engel, James Douglas
author_sort Hosoya, Tomonori
collection PubMed
description Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation steps as well as for the development of thymic natural killer cells. However, a role for GATA-3 before the double-negative (DN) 3 stage of T cell development has to date been obscured both by the developmental heterogeneity of DN1 thymocytes and the paucity of ETPs. We provide multiple lines of in vivo evidence through the analysis of T cell development in Gata3 hypomorphic mutant embryos, in irradiated mice reconstituted with Gata3 mutant hematopoietic cells, and in mice conditionally ablated for the Gata3 gene to show that GATA-3 is required for ETP generation. We further show that Gata3 loss does not affect hematopoietic stem cells or multipotent hematopoietic progenitors. Finally, we demonstrate that Gata3 mutant lymphoid progenitors exhibit neither increased apoptosis nor diminished cell-cycle progression. Thus, GATA-3 is required for the cell-autonomous development of the earliest characterized thymic T cell progenitors.
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spelling pubmed-28064532010-06-21 GATA-3 is required for early T lineage progenitor development Hosoya, Tomonori Kuroha, Takashi Moriguchi, Takashi Cummings, Dustin Maillard, Ivan Lim, Kim-Chew Engel, James Douglas J Exp Med Article Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation steps as well as for the development of thymic natural killer cells. However, a role for GATA-3 before the double-negative (DN) 3 stage of T cell development has to date been obscured both by the developmental heterogeneity of DN1 thymocytes and the paucity of ETPs. We provide multiple lines of in vivo evidence through the analysis of T cell development in Gata3 hypomorphic mutant embryos, in irradiated mice reconstituted with Gata3 mutant hematopoietic cells, and in mice conditionally ablated for the Gata3 gene to show that GATA-3 is required for ETP generation. We further show that Gata3 loss does not affect hematopoietic stem cells or multipotent hematopoietic progenitors. Finally, we demonstrate that Gata3 mutant lymphoid progenitors exhibit neither increased apoptosis nor diminished cell-cycle progression. Thus, GATA-3 is required for the cell-autonomous development of the earliest characterized thymic T cell progenitors. The Rockefeller University Press 2009-12-21 /pmc/articles/PMC2806453/ /pubmed/19934022 http://dx.doi.org/10.1084/jem.20090934 Text en © 2009 Hosoya et al. 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.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Hosoya, Tomonori
Kuroha, Takashi
Moriguchi, Takashi
Cummings, Dustin
Maillard, Ivan
Lim, Kim-Chew
Engel, James Douglas
GATA-3 is required for early T lineage progenitor development
title GATA-3 is required for early T lineage progenitor development
title_full GATA-3 is required for early T lineage progenitor development
title_fullStr GATA-3 is required for early T lineage progenitor development
title_full_unstemmed GATA-3 is required for early T lineage progenitor development
title_short GATA-3 is required for early T lineage progenitor development
title_sort gata-3 is required for early t lineage progenitor development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806453/
https://www.ncbi.nlm.nih.gov/pubmed/19934022
http://dx.doi.org/10.1084/jem.20090934
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