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Deciphering the regulatory landscapte of fetal and adult γδ T-cell development at single-cell resolution

MPS-Authors

Sagar,  Sagar
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Herman,  Josip S
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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

Wegner,  Michael
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

Sagar, S., Pokrovskii, M., Herman, J. S., Naik, S., Sock, E., Zeis, P., et al. (2020). Deciphering the regulatory landscapte of fetal and adult γδ T-cell development at single-cell resolution. The EMBO Journal, 39: e104159. doi:10.15252/embj.2019104159.


Cite as: http://hdl.handle.net/21.11116/0000-0006-A20C-6
Abstract
γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high‐resolution map of γδ T‐cell differentiation from the fetal and adult thymus using single‐cell RNA sequencing. We reveal novel sub‐types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T‐cell differentiation. By performing a combined single‐cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL ‐17‐producing γδ T‐cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T‐cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages.