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

First Author  Sagar Year  2020
Journal  EMBO J Volume  39
Issue  13 Pages  e104159
PubMed ID  32627520 Mgi Jnum  J:297235
Mgi Id  MGI:6441626 Doi  10.15252/embj.2019104159
Citation  Sagar, et al. (2020) Deciphering the regulatory landscape of fetal and adult gammadelta T-cell development at single-cell resolution. EMBO J 39(13):e104159
abstractText  gammadelta 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 gammadelta T cells in the thymus is incompletely understood. Here, we establish a high-resolution map of gammadelta T-cell differentiation from the fetal and adult thymus using single-cell RNA sequencing. We reveal novel sub-types of immature and mature gammadelta 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 gammadelta 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 gammadelta T-cell (gammadeltaT17) differentiation. These findings substantially expand our understanding of gammadelta 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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