Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
|---|---|
| Enthalten in: |
Journal of leukocyte biology - 115(2024), 2 vom: 19. Jan., Seite 401-409 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Maas-Bauer, Kristina [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Differentiation |
|---|
| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 05.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/jleuko/qiad113 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36238536X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36238536X | ||
| 003 | DE-627 | ||
| 005 | 20240305231951.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/jleuko/qiad113 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1317.xml |
| 035 | |a (DE-627)NLM36238536X | ||
| 035 | |a (NLM)37742056 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Maas-Bauer, Kristina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.01.2024 | ||
| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a differentiation | |
| 650 | 4 | |a human invariant natural killer T cells | |
| 650 | 4 | |a iNKT | |
| 650 | 4 | |a iNKT subsets | |
| 650 | 4 | |a scRNAseq | |
| 650 | 4 | |a thymic development | |
| 700 | 1 | |a Köhler, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Stell, Anna-Verena |e verfasserin |4 aut | |
| 700 | 1 | |a Zwick, Melissa |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Swati |e verfasserin |4 aut | |
| 700 | 1 | |a Rensing-Ehl, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a König, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Kroll, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Baker, Jeanette |e verfasserin |4 aut | |
| 700 | 1 | |a Koßmann, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Pradier, Amandine |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Sisi |e verfasserin |4 aut | |
| 700 | 1 | |a Docquier, Mylène |e verfasserin |4 aut | |
| 700 | 1 | |a Lewis, David B |e verfasserin |4 aut | |
| 700 | 1 | |a Negrin, Robert S |e verfasserin |4 aut | |
| 700 | 1 | |a Simonetta, Federico |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of leukocyte biology |d 1986 |g 115(2024), 2 vom: 19. Jan., Seite 401-409 |w (DE-627)NLM012617644 |x 1938-3673 |7 nnns |
| 773 | 1 | 8 | |g volume:115 |g year:2024 |g number:2 |g day:19 |g month:01 |g pages:401-409 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/jleuko/qiad113 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 115 |j 2024 |e 2 |b 19 |c 01 |h 401-409 | ||