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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类别
资金
- Pasteur Foundation
- Huygens Scholarship Program (the Netherlands)
- Royal Netherlands Academy for Arts and Sciences (the Netherlands)
- Ligue Nationale Contre le Cancer in France
- Institut Pasteur in France
- Inserm in France
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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