Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1− T-bet+ intraepithelial lymphocyte precursors
Hummel JF, Zeis P, Ebert K, Fixemer J, Konrad P, Schachtrup C, Arnold SJ, Gruen D, Tanriver Y (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 13
Pages Range: 257-270
Journal Issue: 2
DOI: 10.1038/s41385-019-0220-y
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 CD4−CD8αβ−TCRαβ+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.
Involved external institutions
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Germany (DE)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
How to cite
APA:
Hummel, J.F., Zeis, P., Ebert, K., Fixemer, J., Konrad, P., Schachtrup, C.,... Tanriver, Y. (2020). Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1− T-bet+ intraepithelial lymphocyte precursors. Mucosal Immunology, 13(2), 257-270. https://doi.org/10.1038/s41385-019-0220-y
MLA:
Hummel, Jonas F., et al. "Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1− T-bet+ intraepithelial lymphocyte precursors." Mucosal Immunology 13.2 (2020): 257-270.
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