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

Nat Immunol. 2007 Aug;8(8):845-55. doi: 10.1038/ni1486. Epub 2007 Jul 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology*
  • Cells, Cultured
  • Flow Cytometry
  • GATA3 Transcription Factor / immunology*
  • GATA3 Transcription Factor / metabolism
  • Mast Cells / cytology*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Transgenic
  • Receptors, Notch / immunology
  • Receptors, Notch / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*


  • GATA3 Transcription Factor
  • Receptors, Notch