Thymic epithelial organoids mediate T cell development [scRNA-seq]. Thymic epithelial organoids mediate T cell development [scRNA-seq]

Although the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here we established organoids from the thymus, the lymphoid organ responsible for T cell development. We identified conditions enabling thymic epithelial progenitor cell proliferation and development into organoids with diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. Contrary to these two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T cell development upon reaggregation with T cell progenitors. The reaggregates showed in vivo-like epithelial diversity and ability to attract T cell progenitors. Thymic epithelial organoids are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries. Overall design: Single-cell RNA-seq of organoid reaggreagte fetal thymic organ culture (ORFTOC) and fetal thymic organ culture (FTOC) labeled with HTOs

尽管类器官（organoids）的出现为基础研究与转化研究开辟了前所未有的前景，但免疫系统相关类器官的开发仍远未得到充分开展。本研究从胸腺——负责T细胞发育的淋巴器官——中构建了类器官。我们确定了可促进胸腺上皮祖细胞增殖并分化为类器官的培养条件，此类类器官拥有多样的细胞群与转录谱，相较于传统胸腺上皮细胞（TECs）培养体系，其特征更贴近体内胸腺上皮细胞。与这类二维培养体系不同，胸腺上皮类器官可在体外维持胸腺功能，且在与T细胞祖细胞重聚集后，可介导生理性T细胞发育。此类重聚集体展现出类似体内的上皮细胞多样性，以及招募T细胞祖细胞的能力。胸腺上皮类器官是首个源自淋巴器官基质区室的类器官，为体外研究TEC生物学特性与T细胞发育提供了新的契机，也为衰老或急性损伤后的胸腺再生策略铺平了道路。实验整体设计：对经HTO标记的类器官重聚集胎胸腺器官培养物（ORFTOC）与胎胸腺器官培养物（FTOC）进行单细胞RNA测序。