title: GATA-3 promotes T-cell specification by repressing B-cell potential in pro-T cells in mice.
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.
authors.affiliation: Innate Immunity Unit, Institut Pasteur, Paris, France.
authors.forename: Marcos E
authors.initials: ME
authors.lastname: García-Ojeda
authors.forename: Roel G J
authors.initials: RG
authors.lastname: Klein Wolterink
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.forename: Odile
authors.initials: O
authors.lastname: Richard-Le Goff
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.forename: Rudolf W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051881:Receptor, Notch1 / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors