Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution
Open accessAbstract
Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C + CD301A + myeloid dendritic cell population in psoriatic epidermis, and IL1β hi CCL3 hi CD14 + monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation.
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Human epidermis is more heterogeneous than previously thought.
“human epidermis is more heterogeneous than previously thought.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [29]
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Massively parallel digital transcriptional profiling of single cells
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- Authors
- Cheng, J. B., Sedgewick, A. J., Finnegan, A. I., Harirchian, P., Lee, J., Kwon, S., Fassett, M. S., Golovato, J., Gray, M., Ghadially, R., Liao, W., Perez White, B. E., Mauro, T. M., Mully, T., Kim, E. A., Sbitany, H., Neuhaus, I. M., Grekin, R. C., Yu, S. S., Gray, J. W., Purdom, E., Paus, R., Vaske, C. J., Benz, S. C., Song, J. S., & Cho, R. J.
- Affiliations
- San Francisco VA Medical Center (US)
- NantOmics LLC (United States) (US)
- University of Illinois Urbana-Champaign (US)
- Oregon Health & Science University (US)
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- University of Miami (US)
- Corresponding author
- Cho, Raymond J.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 25
- Issue
- 4
- Pages
- 871-883
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6367716
- OpenAlex
- W2897926103
- Cited by
- 284
- References
- 3
- Citations by year
- 2026: 26 · 2025: 34 · 2024: 43 · 2023: 40 · 2022: 50 · 2021: 33 · 2020: 38 · 2019: 16 · 2018: 3 · 2016: 1
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by)
- PubMed Central (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Funders
- NIH (R01CA163336, K08AR067243)
- Grainger Engineering Breakthroughs Initiative
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- human epidermis, keratinocytes, epidermal differentiation, skin inflammation, psoriasis, myeloid dendritic cells, monocyte-derived macrophages, IL-1β, CCL3, Wnt signaling, intercellular communication, epidermal homeostasis, single-cell transcriptomics, interfollicular epidermis, prepuce, scalp
- MeSH terms
- Cell Aggregation, Cell Communication, Cell Differentiation, Epidermis, Humans, Inflammation, Kinetics, Male, S100 Proteins, Psoriasis, Time Factors, Transcription, Genetic, Biomarkers, Keratinocytes, Hair Follicle, Cell Proliferation, Wnt Proteins, Foreskin, Single-Cell Analysis, Transcriptome, Amphiregulin
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