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

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

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  • 1Innate Immunity Unit, Institut Pasteur, Paris, France.

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.

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PMID:
23287858
[PubMed - indexed for MEDLINE]
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