Transcriptome of LCH lesion CD1a⁺CD207⁺cells is most closely related to blood CD1c⁺mDCs. (A) CMAP analysis score for LCH CD1a⁺CD207⁺ DCs (n = 6) against healthy donor DCs/monocytes/macrophages after removal of tissue-specific genes. Each symbol represents an LCH lesion specimen. All samples used in the study are listed in supplemental Table 3a. A 1000 permutation test among gene signatures was performed on each enrichment score to determine the significance. CMAP scores for LCH CD1a⁺CD207⁺ DCs with all other human myeloid subsets were significant at P < .0001. The CMAP scores indicate the relative “closeness” of LCH CD1a⁺CD207⁺ DCs to myeloid subsets. LCH CD1a⁺CD207⁺ DCs show the highest CMAP scores with CD1c⁺ mDCs, followed by CD141⁺ mDCs and epidermal LCs. (B) Gene signatures of monocyte/DC/macrophage populations were used to compare with the gene-expression data set from LCH lesion CD1a⁺CD207⁺ DCs (n = 6) against the gene-expression data set from human myeloid subsets using BubbleGUM. Gene-expression profiles were obtained from FACS-sorted CD1a⁺CD207⁺ DCs from LCH lesions as well as DC/monocyte populations from healthy donor (HD) skin and peripheral blood specimens. Illumina Human HT-12 V4.0 was used for this study. All samples used in the study are listed in supplemental Table 3a. Blue bubbles represent similarity to the LCH CD1a⁺CD207⁺ transcriptome; red bubbles represent similarity to the comparison transcriptome. The bubble area corresponds to the GSEA normalized enrichment score (NES); the intensity of the color corresponds to the statistical significance of the enrichment. The larger and darker in color the bubble becomes, the more significant the enrichment of the gene signature becomes in that particular class. LCH CD1a⁺CD207⁺ DCs consistently show the highest enrichment (blue) with the CD1c⁺ mDC gene signature when compared with all signatures from other cell types. (C) Unsupervised cluster analysis of LCH lesion CD1a⁺CD207⁺ DCs and healthy donor blood DC/monocyte subsets demonstrates the relationship between LCH lesion CD1a⁺CD207⁺ DCs and healthy donor blood CD1c⁺ mDCs. Gene-expression profiles were obtained from FACS-sorted CD1a⁺CD207⁺ DCs from LCH lesions as well as DC/monocyte populations from healthy donors skin and peripheral blood specimens. Illumina Human HT-12 V4.0 was used for this study. All samples used in the study are listed in supplemental Table 3a. FDR, false discovery rate; NS, not significant.