4.7 Article

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

期刊

BLOOD
卷 121, 期 10, 页码 1749-1759

出版社

AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-06-440065

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资金

  1. Pasteur Foundation
  2. Huygens Scholarship Program (the Netherlands)
  3. Royal Netherlands Academy for Arts and Sciences (the Netherlands)
  4. Ligue Nationale Contre le Cancer in France
  5. Institut Pasteur in France
  6. Inserm in France

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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.

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