ArticlePLoS biology2012
The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate.Science immunology · 2025Article
- Cholinergic regulation of thymocyte negative selection.Nature immunology · 2025Article
- Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.Journal of pathology and translational medicine · 2024Article
- The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology.Cell communication and signaling : CCS · 2024Review
- The multifaceted roles of TCF1 in innate and adaptive lymphocytes.Advances in immunology · 2024Review
- Speed and navigation control of thymocyte development by the fetal T-cell gene regulatory network.Immunological reviews · 2023Review
- The Interplay of Transcription and Genome Topology Programs T Cell Development and Differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Modulation of RNA splicing associated with Wnt signaling pathway using FD-895 and pladienolide B.Aging · 2022Article
- TCF1 in T cell immunity: a broadened frontier.Nature reviews. Immunology · 2022Review
- Transcriptional Regulation of Early T-Lymphocyte Development in Thymus.Frontiers in immunology · 2022Review
- E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Review
- Review
- The Route of Early T Cell Development: Crosstalk between Epigenetic and Transcription Factors.Cells · 2021Review
- How transcription factors drive choice of the T cell fate.Nature reviews. Immunology · 2021Review
- Exploring the stage-specific roles of Tcf-1 in T cell development and malignancy at single-cell resolution.Cellular & molecular immunology · 2021Article
- Functional definition of a transcription factor hierarchy regulating T cell lineage commitment.Science advances · 2020Article
- Loss of MBNL1 induces RNA misprocessing in the thymus and peripheral blood.Nature communications · 2020Article
- The Role Played by Wnt/β-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- Review
- Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs).Scientific reports · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell-specific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.
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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.