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Journal Article

Single-cell RNA-sequencing identifiesthe developmental trajectory of C-Myc-dependent NK1.1-T-bet+

MPS-Authors

Zeis,  Patrice
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grün,  Dominic
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Hummel, J. F., Zeis, P., Fixemer, J., Konrad, P., Schachtrup, C., Arnold, S. J., et al. (2019). Single-cell RNA-sequencing identifiesthe developmental trajectory of C-Myc-dependent NK1.1-T-bet+. Mucosal immunology: official journal of the Society for Mucosal Immunology, 13, 257-270. doi:10.1038/s41385-019-0220-y.


Cite as: http://hdl.handle.net/21.11116/0000-0008-830F-4
Abstract
Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4CD8αβTCRαβ+NK1.1 IEL precursors (NK1.1 IELPs), we define a developmental trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1 IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1 IELPs and deepen our understanding of this still elusive cell type.