Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells
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| Title: | Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells |
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| Authors: | Maas-Bauer, Kristina, Köhler, Natalie, Stell, Anna-Verena, Zwick, Melissa, Acharya, Swati, Rensing-Ehl, Anne, König, Christoph, Kroll, Johannes, Baker, Jeanette, Koßmann, Stefanie, Pradier, Amandine, Wang, Sisi, Docquier, Mylene, Lewis, David B, Negrin, Robert S, Simonetta, Federico |
| Source: | J Leukoc Biol |
| Publisher Information: | Oxford University Press (OUP), 2023. |
| Publication Year: | 2023 |
| Subject Terms: | 576.5, ScRNAseq, Cell Differentiation / genetics, Thymocytes, INKT, Natural Killer T-Cells / metabolism, Brief Report, Gene Expression Profiling, Cell Differentiation, Thymus Gland, Thymic development, Mice, T-Lymphocyte Subsets, Differentiation, Humans, Animals, Natural Killer T-Cells, Human invariant natural killer T cells, INKT subsets |
| Description: | Invariant natural killer T cells are a rare, heterogeneous T-cell subset with cytotoxic and immunomodulatory properties. During thymic development, murine invariant natural killer T cells go through different maturation stages differentiating into distinct sublineages, namely, invariant natural killer T1, 2, and 17 cells. Recent reports indicate that invariant natural killer T2 cells display immature properties and give rise to other subsets, whereas invariant natural killer T1 cells seem to be terminally differentiated. Whether human invariant natural killer T cells follow a similar differentiation model is still unknown. To define the maturation stages and assess the sublineage commitment of human invariant natural killer T cells during thymic development, in this study, we performed single-cell RNA sequencing analysis on human Vα24+Vβ11+ invariant natural killer T cells isolated from thymocytes. We show that these invariant natural killer T cells displayed heterogeneity, and our unsupervised analysis identified 5 clusters representing different maturation stages, from an immature profile with high expression of genes important for invariant natural killer T cell development and proliferation to a mature, fully differentiated profile with high levels of cytotoxic effector molecules. Evaluation of expression of sublineage-defining gene sets revealed mainly cells with an invariant natural killer T2 signature in the most immature cluster, whereas the more differentiated ones displayed an invariant natural killer T1 signature. Combined analysis with a publicly available single-cell RNA sequencing data set of human invariant natural killer T cells from peripheral blood suggested that the 2 main subsets exist both in thymus and in the periphery, while a third more immature one was restricted to the thymus. Our data point to the existence of different maturation stages of human thymic invariant natural killer T cells and provide evidence for sublineage commitment of invariant natural killer T cells in the human thymus. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf; pdf |
| Language: | English |
| ISSN: | 1938-3673 |
| DOI: | 10.1093/jleuko/qiad113 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/37742056 https://archive-ouverte.unige.ch/unige:176686 https://doi.org/10.1093/jleuko/qiad113 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Accession Number: | edsair.doi.dedup.....8d3f669b69dd8c8fa7b9e35f67e2c869 |
| Database: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | Invariant natural killer T cells are a rare, heterogeneous T-cell subset with cytotoxic and immunomodulatory properties. During thymic development, murine invariant natural killer T cells go through different maturation stages differentiating into distinct sublineages, namely, invariant natural killer T1, 2, and 17 cells. Recent reports indicate that invariant natural killer T2 cells display immature properties and give rise to other subsets, whereas invariant natural killer T1 cells seem to be terminally differentiated. Whether human invariant natural killer T cells follow a similar differentiation model is still unknown. To define the maturation stages and assess the sublineage commitment of human invariant natural killer T cells during thymic development, in this study, we performed single-cell RNA sequencing analysis on human Vα24+Vβ11+ invariant natural killer T cells isolated from thymocytes. We show that these invariant natural killer T cells displayed heterogeneity, and our unsupervised analysis identified 5 clusters representing different maturation stages, from an immature profile with high expression of genes important for invariant natural killer T cell development and proliferation to a mature, fully differentiated profile with high levels of cytotoxic effector molecules. Evaluation of expression of sublineage-defining gene sets revealed mainly cells with an invariant natural killer T2 signature in the most immature cluster, whereas the more differentiated ones displayed an invariant natural killer T1 signature. Combined analysis with a publicly available single-cell RNA sequencing data set of human invariant natural killer T cells from peripheral blood suggested that the 2 main subsets exist both in thymus and in the periphery, while a third more immature one was restricted to the thymus. Our data point to the existence of different maturation stages of human thymic invariant natural killer T cells and provide evidence for sublineage commitment of invariant natural killer T cells in the human thymus. |
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| ISSN: | 19383673 |
| DOI: | 10.1093/jleuko/qiad113 |