ArticleCell discovery2023
Integrative scATAC-seq and scRNA-seq analyses map thymic iNKT cell development and identify Cbfβ for its commitment.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- E protein-driven iNKT subset modulation shapes early immune responses during influenza A virus infection.American journal of respiratory cell and molecular biology · 2026Article
- Deciphering the blueprint of life: integrated protocols for single-cell multi-omics and functional genomics.Blood science (Baltimore, Md.) · 2026Article
- Innate-like T Cell Biology in the Tumor Microenvironment Implications for Cancer Immunotherapy.Cells · 2026Review
- Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.Frontiers in immunology · 2026Review
- A drop-based workflow for fast and robust joint profiling of transcriptome and chromatin accessibility in the same cell.Blood science (Baltimore, Md.) · 2025Article
- Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.Cell reports · 2025Article
- Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response.Frontiers in immunology · 2025Review
- Development of a deep learning-based 1D convolutional neural network model for cross-species natural killer T cell identification using peripheral blood mononuclear cell single-cell RNA sequencing data.Veterinary world · 2024Article
- Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models.Cell reports · 2024Article
- Article
- β-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.Vaccines · 2024Article
- Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells.Journal of leukocyte biology · 2024Article
- Insights into the heterogeneity of iNKT cells: tissue-resident and circulating subsets shaped by local microenvironmental cues.Frontiers in immunology · 2024Review
- Hi-C, a chromatin 3D structure technique advancing the functional genomics of immune cells.Frontiers in genetics · 2024Review
- Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Unlike conventional αβT cells, invariant natural killer T (iNKT) cells complete their terminal differentiation to functional iNKT1/2/17 cells in the thymus. However, underlying molecular programs that guide iNKT subset differentiation remain unclear. Here, we profiled the transcriptomes of over 17,000 iNKT cells and the chromatin accessibility states of over 39,000 iNKT cells across four thymic iNKT developmental stages using single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to define their developmental trajectories. Our study discovered novel features for iNKT precursors and different iNKT subsets and indicated that iNKT2 and iNKT17 lineage commitment may occur as early as stage 0 (ST0) by two distinct programs, while iNKT1 commitments may occur post ST0. Both iNKT1 and iNKT2 cells exhibit extensive phenotypic and functional heterogeneity, while iNKT17 cells are relatively homogenous. Furthermore, we identified that a novel transcription factor, Cbfβ, was highly expressed in iNKT progenitor commitment checkpoint, which showed a similar expression trajectory with other known transcription factors for iNKT cells development, Zbtb16 and Egr2, and could direct iNKT cells fate and drive their effector phenotype differentiation. Conditional deletion of Cbfβ blocked early iNKT cell development and led to severe impairment of iNKT1/2/17 cell differentiation. Overall, our findings uncovered distinct iNKT developmental programs as well as their cellular heterogeneity, and identified a novel transcription factor Cbfβ as a key regulator for early iNKT cell commitment.
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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.