Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype
Open accessAbstract
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 HES1, COL11A1, MYL4 and CTNNB1 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.
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HSEs are used to investigate wound healing, aging, and various diseases.
“HSEs are used to investigate various aspects of normal and abnormal skin biology, including wound healing [40,41], aging [42,43], and the study of various diseases [18].”
From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [42]
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- Authors
- Ahlers, J. M. D., Falckenhayn, C., Holzscheck, N., Solé-Boldo, L., Schütz, S., Wenck, H., Winnefeld, M., Lyko, F., Grönniger, E., & Siracusa, A.
- Affiliations
- Beiersdorf (Germany) (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Grönniger, Elke
- ORCID
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2022-01-07
- Volume
- 12
- Pages
- 797747-797747
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC8776708
- OpenAlex
- W4206384540
- Cited by
- 46
- References
- 37
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 12 · 2023: 18 · 2022: 4
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- dermal sheath, skin aging, hair follicle stem cells, dermal stem cells, dermal papilla, stem cell self-renewal, Hes1, COL11A1, CTNNB1, activin A, paracrine signaling, keratinocytes, dermal fibroblasts, epidermal thickness, collagen synthesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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