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

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.

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 Creators:
Sagar, Sagar1, Author
Pokrovskii, Maria2, Author
Herman, Josip S1, Author
Naik, Shruti2, Author
Sock, Elisabeth2, Author
Zeis, Patrice1, Author
Lausch, Ute2, Author
Wegner, Michael1, Author
Tanriver, Yakup2, Author
Littman, Dan R2, Author
Grün, Dominic1, Author           
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1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243642              
2External Organizations, ou_persistent22              

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Free keywords: double negative progenitors, fetal and adult thymus, gamma delta T cells, gamma delta T-cell differentiation, single-cell RNA sequencing
 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.

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Language(s): eng - English
 Dates: 2020-06-082020-07-01
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.15252/embj.2019104159
 Degree: -

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Title: The EMBO Journal
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 39 Sequence Number: e104159 Start / End Page: - Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061_1