Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

T Taghon, MA Yui, EV Rothenberg - Nature immunology, 2007 - nature.com
Nature immunology, 2007nature.com
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 …
Abstract
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.
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