O27 Spatial transcriptomic profiles of photoexposed and photoprotected skin in lighter- and darker-skinned individuals

Abstract Introduction and aims Significant progress has been made in understanding physiological differences between photoexposed and photoprotected skin in healthy human adults, including in different skin types. However, how these may link to transcriptional differences at the single-cell level is unknown. Here, we compared spatial transcriptomic profiles of photoexposed and photoprotected healthy skin from young light- and dark-skinned individuals. Methods Skin punch biopsies were obtained from the forearm (photoexposed) and buttock (photoprotected) of healthy volunteers (aged 22–29 years) of skin type I–II (n = 4) and V–VI (n = 4). Biopsies were cryosectioned and analysed using the Prime 5K panel (5001 genes) on the Xenium In Situ platform (10x Genomics, Pleasanton, CA, USA). Differentially expressed genes (DEGs) (> 0.5 log2 fold change, < 0.05 Q-value) were identified and analysed by Qiagen Ingenuity Pathway Analysis. Results Compared with photoprotected skin, photoexposed skin displayed 464 and 107 DEGs in light- and dark-skinned individuals, respectively. Light, but not dark photoexposed skin exhibited upregulation of chemokines CCL22 and CCL19, and matrix metalloproteinase 9, and downregulation of transcription factor NR4A1, a regulator of the cell cycle and inflammation. Pathways associated with collagen and extracellular matrix degradation were enriched in both light and dark photoexposed skin. Enrichment of pathways involved in proinflammatory signalling, oxidative stress, and senescence were observed exclusively in light photoexposed skin. DEGs associated with senescence and oxidative stress pathways were expressed in multiple cell types across the epidermis and dermis. Conclusions Our findings demonstrate that photoexposed skin of young light-skinned individuals exhibits a distinct inflammatory profile compared with photoprotected regions. Moreover, photoexposed darker skin did not display the cellular senescence and oxidative stress transcriptomic profile observed in lighter skin, suggesting an intrinsically lower oxidative stress status. These differences may link to the structural and functional differences seen in photoexposed and photoprotected skin in different skin types.