ArticleGenome medicine2021
Development of double-positive thymocytes at single-cell resolution.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 38 citations in OpenAlex.
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- Aire-dependent interferon signalling shapes thymocyte maturation and central tolerance in mice.Communications biology · 2025Article
- Double-positive T cells form heterotypic clusters with circulating tumor cells to foster cancer metastasis.The Journal of clinical investigation · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Aging and immunity: the age-old tango.Genes & development · 2025Review
- Gene-regulatory programs that specify age-related differences during thymocyte development.Cell reports · 2025Article
- Article
- Comparative transcriptomic analyses of thymocytes using 10x Genomics and Parse scRNA-seq technologies.BMC genomics · 2024Article
- Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling.Nature communications · 2024Article
- Protective effects ofFrontiers in pharmacology · 2024Article
- An integrative mechanistic model of thymocyte dynamics.Frontiers in immunology · 2024Article
- Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection.Frontiers in immunology · 2024Article
- Protein-level mutant p53 reporters identify druggable rare precancerous clones in noncancerous tissues.Nature cancer · 2023Article
- RNA helicase DHX15 exemplifies a unique dependency in acute leukemia.Haematologica · 2023Article
- Tox4 regulates transcriptional elongation and reinitiation during murine T cell development.Communications biology · 2023Article
- The transcriptional regulator Sin3A balances IL-17A and Foxp3 expression in primary CD4 T cells.EMBO reports · 2023Article
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- Characterization of fetal microchimeric immune cells in mouse maternal hearts during physiologic and pathologic pregnancies.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated.
methodsWe applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat. By applying unsupervised clustering, we defined thymocyte subtypes and validated DP cell subtypes by flow cytometry. We classified the cell cycle phases of each cell according to expression of cell cycle phase-specific genes. For immune synapse detection, we used immunofluorescent staining and ImageStream-based flow cytometry. We studied and integrated human thymocyte data to verify the conservation of our findings and also performed cross-species comparisons to examine species-specific gene regulation.
resultsWe classified blast, rearrangement, and selection subtypes of DP thymocytes and used the surface markers CD2 and Ly6d to identify these subtypes by flow cytometry. Based on this new classification, we found that the proliferation of blast DP cells is quite different from that of double-positive cells and other cell types, which tend to exit the cell cycle after a single round. At the DP cell selection stage, we observed that CD8-associated immune synapses formed between thymocytes, indicating that CD8sp selection occurred among thymocytes themselves. Moreover, cross-species comparison revealed species-specific transcription factors (TFs) that contribute to the transcriptional differences of thymocytes from humans and mice.
conclusionsOur study classified DP thymocyte subtypes of different developmental stages and provided new insight into the development of DP thymocytes at single-cell resolution, furthering our knowledge of the fundamental immunological process of thymopoiesis.
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