@article{10.1172/jci.insight.159762, author = {Alexander A. Merleev AND Stephanie T. Le AND Claire Alexanian AND Atrin Toussi AND Yixuan Xie AND Alina I. Marusina AND Steven M. Watkins AND Forum Patel AND Allison C. Billi AND Julie Wiedemann AND Yoshihiro Izumiya AND Ashish Kumar AND Ranjitha Uppala AND J. Michelle Kahlenberg AND Fu-Tong Liu AND Iannis E. Adamopoulos AND Elizabeth A. Wang AND Chelsea Ma AND Michelle Y. Cheng AND Halani Xiong AND Amanda Kirane AND Guillaume Luxardi AND Bogi Andersen AND Lam C. Tsoi AND Carlito B. Lebrilla AND Johann E. Gudjonsson AND Emanual Maverakis}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes}, year = {2022}, month = {8}, volume = {7}, url = {https://insight.jci.org/articles/view/159762}, abstract = {The epidermis is the outermost layer of skin. Here, we used targeted lipid profiling to characterize the biogeographic alterations of human epidermal lipids across 12 anatomically distinct body sites, and we used single-cell RNA-Seq to compare keratinocyte gene expression at acral and nonacral sites. We demonstrate that acral skin has low expression of EOS acyl-ceramides and the genes involved in their synthesis, as well as low expression of genes involved in filaggrin and keratin citrullination (PADI1 and PADI3) and corneodesmosome degradation, changes that are consistent with increased corneocyte retention. Several overarching principles governing epidermal lipid expression were also noted. For example, there was a strong negative correlation between the expression of 18-carbon and 22-carbon sphingoid base ceramides. Disease-specific alterations in epidermal lipid gene expression and their corresponding alterations to the epidermal lipidome were characterized. Lipid biomarkers with diagnostic utility for inflammatory and precancerous conditions were identified, and a 2-analyte diagnostic model of psoriasis was constructed using a step-forward algorithm. Finally, gene coexpression analysis revealed a strong connection between lipid and immune gene expression. This work highlights (a) mechanisms by which the epidermis is uniquely adapted for the specific environmental insults encountered at different body surfaces and (b) how inflammation-associated alterations in gene expression affect the epidermal lipidome.}, number = {16}, doi = {10.1172/jci.insight.159762}, url = {https://doi.org/10.1172/jci.insight.159762}, }