Troy/Tnfrsf19 marks epidermal cells that govern interfollicular epidermal renewal and cornification

The skin epidermis is a highly compartmentalised tissue consisting of a cornifying epithelium called the interfollicular epidermis (IFE) and associated hair follicles (HFs). Several stem cell populations have been described that mark specific sub compartments in the skin but none of them is IFE-specific. Here we identify Troy as a marker of IFE and HF infundibulum basal layer cells in embryonic and adult human and mouse epidermis. Genetic lineage-tracing experiments demonstrate that Troy-expressing basal cells contribute to long-term renewal of all layers of the cornifying epithelium. Single-cell transcriptomics and organoid assays of Troy-expressing cells as well as their progeny confirmed stem cell identity as well as the ability to generate differentiating daughter cells. In conclusion, we define Troy as a marker of epidermal basal cells that govern interfollicular epidermal renewal and cornification. We generated single-cell and bulk transcriptome data from epidermal keratinocytes collected from adult murine skin epidermis.

皮肤表皮是一类高度区室化的组织，由被称为表皮间区（interfollicular epidermis, IFE）的角化上皮及其相关的毛囊（hair follicles, HFs）构成。目前已有研究报道了多种可标记皮肤特定亚区室的干细胞群，但尚无针对表皮间区的特异性标记物。本研究鉴定出Troy可作为胚胎及成人皮肤表皮中人源和鼠源表皮基底层细胞的标记物，这类细胞同时分布于表皮间区及毛囊漏斗部。遗传谱系示踪实验证实，表达Troy的基底层细胞可长期维持角化上皮全层的自我更新。对表达Troy的细胞及其子代细胞开展单细胞转录组测序与类器官实验后，验证了其干细胞特性以及产生分化子代细胞的能力。综上，本研究将Troy确定为可调控表皮间区更新与角化的表皮基底层细胞标记物。我们从成年小鼠皮肤表皮分离得到的表皮角质形成细胞中，生成了单细胞及批量转录组数据。