ArticleNature immunology2014
TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells.
Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 187 citations in OpenAlex.
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- Accurate, sensitive, and efficient chromatin accessibility quantification at target loci using UNIChro-seq.Nature communications · 2026Article
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- Integrative, high-resolution analysis of single-cell gene expression across experimental conditions with PARAFAC2-RISE.Cell systems · 2025Article
- Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice.Nature communications · 2025Article
- A microRNA-regulated transcriptional state defines intratumoral CD8Cell reports · 2025Article
- Refining Diagnostic Subtypes of Peripheral T-Cell Lymphoma Using a Multiparameter Approach.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- PRR enhances anti-tumor immunity and suppresses colitis by promoting the development and survival of naive T and iNKT cells.Frontiers in immunology · 2025Article
- A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.Nature immunology · 2024Article
- TCF1 dosage determines cell fate during T cell development.Science advances · 2024Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4(+)CD8(+) double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells and redirected CD4(+) T cells to a CD8(+) T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8(+) lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4(+) T cell fate and establish CD8(+) T cell identity.
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Registered trials
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.