Single-cell RNA profiling of human skin reveals age-related loss of dermal sheath cells and their contribution to a juvenile phenotype

The mesenchyme-derived hair follicle dermal sheath has gained increasing attention because it is thought to include hair follicle dermal stem cells. While the mouse dermal sheath has been studied in considerable detail, very little is known about the human dermal sheath. Here we have used single-cell RNA sequencing to analyze 72,048 cells, including 50,177 fibroblasts from human skin of young and old donors. Our results demonstrate that human dermal sheath cells display stem cell characteristics and are lost upon aging. HES1, COL11A1, MYL4 and CTNNB1 regulate stem cell characteristics of the dermal sheath. Furthermore, we show that Activin A, a dermal sheath secreted protein, shows keratinocytes and dermal fibroblasts. It promotes epidermal thickness and dermal pro-collagen production. Our work thus provides an in-depth description of human dermal sheath on the single-cell level, its loss upon aging, its stem cell characteristics and its contribution to a juvenile skin phenotype.

间充质来源的毛囊真皮鞘（mesenchyme-derived hair follicle dermal sheath）因被认为包含毛囊真皮干细胞而受到越来越多的关注。尽管小鼠真皮鞘已得到相当详尽的研究，但人们对人类真皮鞘的了解却极为有限。本研究利用单细胞RNA测序（single-cell RNA sequencing）技术，分析了72048个细胞，其中包括来自年轻与老年供体的人皮肤组织中的50177个成纤维细胞。研究结果表明，人类真皮鞘细胞具有干细胞特性，且会在衰老过程中发生丢失。HES1、COL11A1、MYL4及CTNNB1可调控真皮鞘的干细胞特性。此外，本研究发现激活素A（Activin A）作为一种真皮鞘分泌蛋白，可作用于角质形成细胞与真皮成纤维细胞，能够促进表皮厚度增加及真皮前胶原生成。综上，本研究从单细胞层面深入阐释了人类真皮鞘的特征、其随衰老发生的丢失现象、干细胞特性，以及其对幼年皮肤表型的贡献。