T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling

Kristine Germar, Marei Dose, Tassos Konstantinou, Jiangwen Zhang, Hongfang Wang, Camille Lobry, Kelly L. Arnett, Stephen C. Blacklow, Iannis Aifantis, Jon C. Aster, Fotini Gounari

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)20060-20065
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 13 2011

ASJC Scopus subject areas

  • General


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