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

ME García-Ojeda, RGJ Klein Wolterink… - Blood, The Journal …, 2013 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2013ashpublications.org
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 …
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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