ArrayExpress Uploader06679Tcf1-/-Tcf1-/-Tcf1-/-wild typewild typewild typearrayexpress_sid6Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and...22109558E-GEOD-33513/profile/8773/arrayexpressuploader16cellnotchproteinstromathymocyteDec.12, 2014Falset-cell-factor-1-is-a-gatekeeper-for-t-cell-specifiE-GEOD-33513_A-AFFY-45T cell factor 1 is a gatekeeper for T-cell specification in response to Notch signalingNov.12, 2014Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/ orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA binding protein Tcf-1, a T-cell specific mediator of Wnt signaling. Yet the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate. We show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of Tcell determination for progression beyond the early thymic progenitor (ETP) stage. The global expression profile of Tcf-1 deficient progenitors indicates that basic processes of DNA metabolism are downregulated in its absence and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development. We used microarrays to detail the global programme of gene expression of mouse ETP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage. 6 samples (mouse ETP thymocytes from wt, and Tcf1 inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0,http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-33513mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-33513/samples/