GATA-3 promotes T cell specification by repressing B cell potential in pro-T cells

Marcos E. García-Ojeda, Roel G.J. Klein Wolterink, Fabrice Lemaître, Odile Richard-Le Goff, Milena Hasan, Rudolf W. Hendriks, Ana Cumano and James P. Di Santo

Key points

  • Gata3 critical for the DN1 to DN2 transition

  • Gata3 represses a latent B cell potential in DN thymocytes


Transcription factors orchestrate T-lineage differentiation in the thymus. One critical checkpoint involves Notch1 signaling that instructs T-cell commitment at the expense of the B-lineage program. While GATA-3 is required for T cell specification, its mechanism of action is poorly understood. Here we show that GATA-3 works in concert with Notch1 to commit thymic progenitors to the T-cell lineage via two distinct pathways. First, GATA-3 orchestrates a transcriptional repertoire that is required for thymocyte maturation up to and beyond the pro-T-cell stage. Second, GATA-3 critically suppresses a latent B-cell potential in pro-T-cells. As such, GATA-3 is essential to seal Notch-induced T-cell fate in early thymocyte precursors by promoting T cell identity through repression of alternative developmental options.

  • Submitted June 28, 2012.
  • Accepted December 4, 2012.