ArticleProceedings of the National Academy of Sciences of the United States of America2011
T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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133 citing papers in PubMed, 213 citations in OpenAlex.
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- The role of TCF-1+CD8+ exhausted progenitors and TCF-1 in graft-versus-host responses.JCI insight · 2025Article
- Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate.Science immunology · 2025Article
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- A timed epigenetic switch balances T and ILC lineage proportions in the thymus.Development (Cambridge, England) · 2024Article
- TCF1 dosage determines cell fate during T cell development.Science advances · 2024Article
- Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024Review
- Multimodal profiling reveals site-specific adaptation and tissue residency hallmarks of γδ T cells across organs in mice.Nature immunology · 2024Article
- LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy.Journal for immunotherapy of cancer · 2024Article
- Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk.Genes & diseases · 2024Review
- The multifaceted roles of TCF1 in innate and adaptive lymphocytes.Advances in immunology · 2024Review
- High density of TCF1+ stem-like tumor-infiltrating lymphocytes is associated with favorable disease-specific survival in NSCLC.Frontiers in immunology · 2024Article
- Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.Thoracic cancer · 2023Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.