Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3.
GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non-T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro-T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro-T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity.
Taghon
Tom
T
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium.
Yui
Mary A
MA
Rothenberg
Ellen V
EV
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D050990:GATA3 Transcription Factor; D051880:Receptors, Notch