Deciphering the regulatory landscape of fetal and adult [gamma delta] T‐cell development at single‐cell resolution

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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
The EMBO journal. - 39, 13 (2020) , e104159, ISSN: 1460-2075

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2020
Creator
Sagar, Stephen
Pokrovskii, Maria
Herman, Josip S.
Naik, Shruti
Sock, Elisabeth
Zeis, Patrice
Lausch, Ute
Wegner, Michael
Tanriver, Yakup
Littman, Dan R.
Grün, Dominic

DOI
10.15252/embj.2019104159
URN
urn:nbn:de:bsz:25-freidok-1671658
Rights
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Last update
14.08.2025, 11:03 AM CEST

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Time of origin

  • 2020

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