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.

中文翻译：

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以单细胞分辨率解读胎儿和成人γδT细胞发育的调控格局。

具有独特特性的γδT细胞在胚胎和成年胸腺中发育，并已被确定为广泛感染，抗肿瘤监测，自身免疫性疾病和组织动态平衡的关键参与者。尽管它们具有免疫治疗的潜在价值，但对胸腺中γδT细胞的分化尚不完全了解。在这里，我们使用单细胞RNA测序建立了从胎儿和成年胸腺的γδT细胞分化的高分辨率图。我们揭示了未成熟和成熟的γδT细胞的新亚型，并鉴定了在血液和淋巴结中扩展的非极化胸腺细胞群。我们详细的比较分析揭示了在胎儿和成人γδT细胞分化过程中活跃的基因网络之间的显着相似性。通过执行组合的单细胞分析Sox13，Maf和Rorc敲除小鼠，我们证明了这些因子在产生IL-17的γδT细胞（γδT17）分化过程中的顺序激活。这些发现大大扩展了我们对胎儿和成人生活中γδT细胞个体发育的理解。我们的实验和计算策略为比较整个发育阶段的免疫细胞分化提供了一个蓝图。