Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Marcos E. García-Ojeda1,
  2. Roel G.J. Klein Wolterink2,
  3. Fabrice Lemaître3,
  4. Odile Richard-Le Goff1,
  5. Milena Hasan4,
  6. Rudolf W. Hendriks5,
  7. Ana Cumano6, and
  8. James P. Di Santo1,*
  1. 1 Innate Immunity Unit, Institut Pasteur, Paris, France;
  2. 2 Inserm U668, Paris, France;
  3. 3 Immune Response Dynamics Unit, Institut Pasteur, Paris, France;
  4. 4 Center for Human Immunology, Institut Pasteur, Paris, France;
  5. 5 Department of Pulmonary Medicine, Erasmus MC Rotterdam, Rotterdam, Netherlands;
  6. 6 Lymphocyte Development Unit, Institut Pasteur, Paris, France
  1. * Corresponding author; email: disanto{at}pasteur.fr

Key points

  • Gata3 critical for the DN1 to DN2 transition

  • Gata3 represses a latent B cell potential in DN thymocytes

Abstract

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.