title: T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling.
abstract: Although 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 T-cell factor 1 (Tcf-1), a T-cell-specific mediator of Wnt signaling. However, 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 and show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of T-cell determination for progression beyond the early thymic progenitor stage. The global expression profile of Tcf-1-deficient progenitors indicates that basic processes of DNA metabolism are down-regulated 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.
authors: Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors: Kristine
authors: K
authors: Germar
authors: Marei
authors: M
authors: Dose
authors: Tassos
authors: T
authors: Konstantinou
authors: Jiangwen
authors: J
authors: Zhang
authors: Hongfang
authors: H
authors: Wang
authors: Camille
authors: C
authors: Lobry
authors: Kelly L
authors: KL
authors: Arnett
authors: Stephen C
authors: SC
authors: Blacklow
authors: Iannis
authors: I
authors: Aifantis
authors: Jon C
authors: JC
authors: Aster
authors: Fotini
authors: F
authors: Gounari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage / Q000276:immunology*; D002465:Cell Movement; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D051822:T Cell Transcription Factor 1 / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology
chemical_list: D051880:Receptors, Notch; D051822:T Cell Transcription Factor 1; D019009:Proto-Oncogene Proteins c-kit