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Publication : GATA-3 is required for early T lineage progenitor development.

First Author  Hosoya T Year  2009
Journal  J Exp Med Volume  206
Issue  13 Pages  2987-3000
PubMed ID  19934022 Mgi Jnum  J:155686
Mgi Id  MGI:4415096 Doi  10.1084/jem.20090934
Citation  Hosoya T, et al. (2009) GATA-3 is required for early T lineage progenitor development. J Exp Med 206(13):2987-3000
abstractText  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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