Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype

The study utilized single-cell RNA sequencing to analyze 72,048 cells from human skin biopsies of various ages, focusing on the dermal sheath (DS) cells, which are crucial for skin homeostasis and include hair follicle dermal stem cells. It was found that DS cells with stem cell characteristics were lost with aging. Key regulators of DS stem cell characteristics were identified as HES1, COL11A1, MYL4, and CTNNB1. Additionally, the DS secreted protein Activin A was shown to have paracrine effects, enhancing keratinocyte and dermal fibroblast proliferation, epidermal thickness, and pro-collagen production, contributing to a juvenile skin phenotype. This research provided a comprehensive understanding of the human DS at the single-cell level, highlighting its decline with age and its role in maintaining youthful skin.