Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype.
Juliane M D Ahlers, Cassandra Falckenhayn, Nicholas Holzscheck, Llorenç Solé-Boldo, Sabrina Schütz, Horst Wenck, Marc Winnefeld, Frank Lyko, Elke Grönniger, Annette Siracusa
Author Information
Juliane M D Ahlers: Beiersdorf AG, Research and Development, Hamburg, Germany.
Cassandra Falckenhayn: Beiersdorf AG, Research and Development, Hamburg, Germany.
Nicholas Holzscheck: Beiersdorf AG, Research and Development, Hamburg, Germany.
Llorenç Solé-Boldo: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Sabrina Schütz: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Horst Wenck: Beiersdorf AG, Research and Development, Hamburg, Germany.
Marc Winnefeld: Beiersdorf AG, Research and Development, Hamburg, Germany.
Frank Lyko: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Elke Grönniger: Beiersdorf AG, Research and Development, Hamburg, Germany.
Annette Siracusa: Beiersdorf AG, Research and Development, Hamburg, Germany.
The dermal sheath (DS) is a population of mesenchyme-derived skin cells with emerging importance for skin homeostasis. The DS includes hair follicle dermal stem cells, which exhibit self-renewal and serve as bipotent progenitors of dermal papilla (DP) cells and DS cells. Upon aging, stem cells exhibit deficiencies in self-renewal and their number is reduced. While the DS of mice has been examined in considerable detail, our knowledge of the human DS, the pathways contributing to its self-renewal and differentiation capacity and potential paracrine effects important for tissue regeneration and aging is very limited. Using single-cell RNA sequencing of human skin biopsies from donors of different ages we have now analyzed the transcriptome of 72,048 cells, including 50,149 fibroblasts. Our results show that DS cells that exhibit stem cell characteristics were lost upon aging. We further show that , , and regulate DS stem cell characteristics. Finally, the DS secreted protein Activin A showed paracrine effects on keratinocytes and dermal fibroblasts, promoting proliferation, epidermal thickness and pro-collagen production. Our work provides a detailed description of human DS identity on the single-cell level, its loss upon aging, its stem cell characteristics and its contribution to a juvenile skin phenotype.
