Epithelial Stem Cell Biology & Regenerative Medicine Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Institute of Immunity & Transplantation, Division of Infection & Immunity, UCL, Pears Building, Rosslyn Hill, London NW3 2PP, UK.
Bioinformatics & Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Dev Cell. 2023 Nov 20;58(22):2428-2446.e9. doi: 10.1016/j.devcel.2023.08.017. Epub 2023 Aug 30.
Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity and undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive immunity. By characterizing cortical and medullary compartments in the human thymus at single-cell resolution, in this study we have defined specific epithelial populations, including those that share properties with bona fide stem cells (SCs) of lifelong regenerating epidermis. Thymic epithelial SCs display a distinctive transcriptional profile and phenotypic traits, including pleiotropic multilineage potency, to give rise to several cell types that were not previously considered to have shared origin. Using here identified SC markers, we have defined their cortical and medullary niches and shown that, in vitro, the cells display long-term clonal expansion and self-organizing capacity. These data substantively broaden our knowledge of SC biology and set a stage for tackling thymic atrophy and related disorders.
胸腺对于终生免疫耐受和免疫至关重要。它表现出独特的上皮复杂性，并随年龄增长而发生萎缩。尽管如此，它也保持着再生能力，如果得到适当的利用，可能允许适应性免疫的年轻化。通过以单细胞分辨率对人类胸腺的皮质和髓质隔室进行特征描述，在这项研究中，我们定义了特定的上皮群体，包括那些与终身再生表皮的真正干细胞（SCs）具有共同特性的群体。胸腺上皮干细胞具有独特的转录谱和表型特征，包括多能性多谱系潜力，能够产生以前不认为具有共同起源的几种细胞类型。使用在这里鉴定的干细胞标记物，我们已经定义了它们的皮质和髓质生态位，并表明在体外，这些细胞具有长期的克隆扩增和自我组织能力。这些数据实质性地扩展了我们对干细胞生物学的认识，并为解决胸腺萎缩和相关疾病奠定了基础。
