ArticleNature immunology2022
A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and β-selection.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Adenosine signaling promotes double-negative T-cell anticancer responses in conditions of CD8 T-cell lymphopenia.Blood immunology & cellular therapy · 2026Article
- Genetic susceptibility ofGlobal medical genetics · 2025Article
- Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate.Science immunology · 2025Article
- A feedback amplifier circuit with Notch and E2A orchestrates T-cell fate and suppresses the innate lymphoid cell lineages during thymic ontogeny.Genes & development · 2025Article
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Enhancers in T Cell development and malignant lesions.Cell death discovery · 2024Review
- Myeloid sarcoma with plasmacytoid dendritic cell-like proliferation associated with IKZF1, ETV6 and DNMT3A mutations.International journal of hematology · 2024Article
- Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.Leukemia · 2024Article
- Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.Blood · 2023Article
- Regulation of immune cell development, differentiation and function by stromal Notch ligands.Current opinion in cell biology · 2023Review
- Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
T cell differentiation requires Notch1 signaling. In the present study, we show that an enhancer upstream of Notch1 active in double-negative (DN) mouse thymocytes is responsible for raising Notch1 signaling intrathymically. This enhancer is required to expand multipotent progenitors intrathymically while delaying early differentiation until lineage restrictions have been established. Early thymic progenitors lacking the enhancer show accelerated differentiation through the DN stages and increased frequency of B, innate lymphoid (IL) and natural killer (NK) cell differentiation. Transcription regulators for T cell lineage restriction and commitment are expressed normally, but IL and NK cell gene expression persists after T cell lineage commitment and T cell receptor β VDJ recombination, Cd3 expression and β-selection have been impaired. This Notch1 enhancer is inactive in double-positive (DP) thymocytes. Its aberrant reactivation at this stage in Ikaros mutants is required for leukemogenesis. Thus, the DN-specific Notch1 enhancer harnesses the regulatory architecture of DN and DP thymocytes to achieve carefully orchestrated changes in Notch1 signaling required for early lineage restrictions and normal T cell differentiation.
Indexed as
Identifiers
What OpenQuestion holds
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.