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 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.
Hosoya
Tomonori
T
Department of Cell and Developmental Biology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kuroha
Takashi
T
Moriguchi
Takashi
T
Cummings
Dustin
D
Maillard
Ivan
I
Lim
Kim-Chew
KC
Engel
James Douglas
JD
D000818:Animals; D019070:Cell Lineage; D050990:GATA3 Transcription Factor / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000196:embryology; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000196:embryology
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse