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

January 2022 in “ Frontiers in Genetics ”

J Ahlers, Cassandra Falckenhayn, Nicholas Holzscheck, Llorenç Solé‐Boldo, Sabrina Schütz, Horst Wenck, Marc Winnefeld, Frank Lyko, Elke Grönniger, Annette Siracusa

dermal sheath cells hair follicle dermal stem cells HES1 COL11A1 MYL4 CTNNB1 Activin A keratinocyte dermal fibroblast epidermal thickness pro-collagen stem cells collagen

TLDR Aging reduces dermal sheath cells, affecting youthful skin appearance.

The study used single-cell RNA sequencing to analyze 72,048 skin cells from 3 young and 4 old Caucasian female participants, revealing that dermal sheath (DS) cells with stem cell characteristics declined with age, contributing to skin aging. Key DS-related genes, such as HES1, COL11A1, MYL4, and CTNNB1, were identified as regulators of stem cell features. DS cells were found to secrete proteins like Activin A, which enhanced keratinocyte proliferation and fibroblast collagen production, promoting a youthful skin appearance. These findings highlighted the potential of targeting DS cells for anti-aging therapies.

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