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

Blood. 2013 Mar 7;121(10):1749-59. doi: 10.1182/blood-2012-06-440065. Epub 2013 Jan 3.

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. We show that GATA-3 works in concert with Notch1 to commit thymic progenitors to the T-cell lineage via 2 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 sealing in Notch-induced T-cell fate in early thymocyte precursors by promoting T-cell identity through the repression of alternative developmental options.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology*
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • GATA3 Transcription Factor / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Receptor, Notch1 / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / embryology
  • Thymus Gland / immunology
  • Transcription Factors / metabolism

Substances

  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors