A Targeted Spatial Transcriptomics Framework for a High-Resolution Human Skin Cell Atlas

Human skin comprises diverse epithelial, mesenchymal, immune and appendage-associated cell populations organised within structured spatial niches. Whilst single-cell RNA sequencing defines transcriptional states, it lacks spatial resolution and accurate mapping within intact tissue. Here, we introduce a high-resolution spatial single-cell profiling framework for human skin to achieve comprehensive cellular annotation in situ. This approach resolves transcriptionally similar and low-abundance populations across epidermal, dermal and appendage compartments, including basal and suprabasal keratinocytes, fibroblast subsets, melanocytes, endothelial and mural cells, and resident immune populations. In skin exposed to inflammatory ultraviolet irradiation, the platform delineates the immune infiltrate at single-cell resolution and captures Langerhans cell egress from the epidermis, demonstrating its capacity to resolve dynamic tissue responses. By improving sensitivity, spatial fidelity and cross-compartment coverage, this framework provides a scalable reference atlas of human skin and establishes a foundation for mechanistic interrogation of tissue organisation, niche interactions and inflammatory remodelling.