Identification of heterogenous CD207⁺CD1A⁺ subclusters in LCH skin. (A) UMAP visualization of cell clusters identified in CD45⁺ cells sorted from epidermal samples from 4 LCH patients (i) and CD45⁺and CD45⁺CD207⁺CD1a⁺ cells from epidermis of 3 healthy donors (ii). (B) Dot plot showing the average expression level and percentage of cells expressing the curated genes in each cluster. (C) Heatmap showing the expression of top 5 DEGs between different clusters identified in epidermis. DEGs are detected using functions tl.rank_gene_groups and tl.filter_rank_gene_groups in Scanpy (Wilcoxon-rank-sum test, with P value adjusted for multiple testing using Benjamini-Hochberg correction); genes with log-fold changes >1 and adjusted P < .05 were selected. (D) Boxplots showing expression of DEGs related to RAS-MAPK-ERK cascade among 4 LC clusters. (E) Heatmap showing the comparison of P values of RAS-MAPK-ERK related pathways among 4 LC subclusters. Each cell is scored for the RAS-MAPK-ERK related pathways using ssGSEA. Differences between groups are compared with Wilcoxon-rank-sum test, and P < .05 is considered to be statistically significant. (F) Correlation matrix showing the correlation coefficient between each cluster identified in skin and blood of LCH patients using complete method. Spearman correlation coefficient is calculated using genes with average expression >0.5.