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

Autor: Sagar; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Pokrovskii M; Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA., Herman JS; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; International Max Planck Research School for Molecular and Cellular Biology (IMPRS-MCB), Freiburg, Germany., Naik S; Department of Pathology and Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, NY, USA., Sock E; Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Zeis P; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; International Max Planck Research School for Molecular and Cellular Biology (IMPRS-MCB), Freiburg, Germany., Lausch U; Institute of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany., Wegner M; Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Tanriver Y; Institute of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany.; Department of Internal Medicine IV, University Medical Center Freiburg, Freiburg, Germany., Littman DR; Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA.; The Howard Hughes Medical Institute, New York University School of Medicine, New York, NY, USA., Grün D; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.; CIBSS-Centre for Integrative Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2020 Jul 01; Vol. 39 (13), pp. e104159. Date of Electronic Publication: 2020 Jun 08.
DOI: 10.15252/embj.2019104159
Abstrakt: 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.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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