ArticleMolecular systems biology2022
Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses.
Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- HPV8-E6 drives coordinated transcriptional and epigenetic reprogramming of keratinocytes.Tumour virus research · 2026Article
- Integrated spatial multi-omics delineates fatty acid degradation fuels malignant evolution at the tumour periphery in cervical squamous cell carcinoma.EBioMedicine · 2026Article
- Non-invasive epidermis sampling for DNA methylation-based prediction of skin cancer phenotypes.NPJ precision oncology · 2026Article
- Multi-omics analysis reveals the crosstalk of epigenetic regulatory networks in cutaneous squamous cell carcinoma progression.Journal of translational medicine · 2025Article
- estiMAge: development of a DNA methylation clock to estimate the methylation age of single cells.Bioinformatics advances · 2025Article
- Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization.Cell death and differentiation · 2025Review
- A molecular mechanism for bright color variation in parrots.Science (New York, N.Y.) · 2024Article
- Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic Cells.The Journal of investigative dermatology · 2023Article
- Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses.Molecular systems biology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell multi-omics, transcriptomics, and methylomics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~3,800 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell-type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the phenotypic traits of the subclasses and the study of additional unstratified KC entities uncovered distinct clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.