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.