Single-cell transcriptomic landscape of keratinocyte transformation from actinic keratosis to skin carcinoma.

ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) develops through a stepwise progression from normal skin (NS) to actinic keratosis (AK) and invasive carcinoma. To delineate the cellular and molecular events underlying this transition, we perform single-cell RNA sequencing on 65,485 cells from NS, AK, and cSCC tissues. The analysis revealed dynamic remodeling of keratinocyte, T cell, and B cell populations during disease progression. A progressively expanding KRT6A ⁺ KRT16 ⁺ keratinocyte subpopulation (Ker-6) displayed an increasing copy number variation burden and activation of tumor-associated pathways. Ligand-receptor analysis indicated that Ker-6 keratinocytes engage proliferative T cells via the interleukin (IL)-13/IL13RA1/IL4R signaling axis. Functi

SUBMITTER: Xu T 

PROVIDER: S-EPMC12723273 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature