Figure 1
Figure 1. LCH cells form a distinct entity among indigenous human DCs. (A-B) LCH cell purification. Cell suspensions obtained from LCH biopsies carried out at the time of diagnosis contain a high number of LCH cells identified by CD1a expression and forward scatter properties. LCH cells were sorted to > 95% purity and reanalyzed for CD1a and Langerin expression. (C) Principal component analysis of LCH cells and 3 indigenous DC subsets. LCs and mDC1s cells are approximately equidistant from LCH cells, although in different axes (dimensions) of the gene space (ie, different gene sets separate LCH from LCs and mDCs). Each DC subset sample is presented by a triangle. LCs, mDC1s, and pDCs (n = 3 for each subset) were isolated from healthy subjects; LCH cells (n = 8) were isolated as shown in panel A. Because of superimpositions, not all symbols can be optically discerned in the displayed figure. (D) Similarity of LCH cells to indigenous DCs. Mean Pearson correlation coefficients of each replicate of LCs, mDC1s, pDCs, and LCH cells versus each replicate of LCH cells are depicted. Correlation coefficients are the highest among LCH samples, followed by mDC1s and LCs, indicating the highest similarity among LCH samples followed by virtually equal similarity of LCH cells to mDC1s and LCs. Results are shown as box plots displaying the medians and 25th and 75th percentiles as boxes and outliers as whiskers. (E-G) Identification of LCH transcripts selectively regulated compared with individual indigenous DC subsets. Volcano plot analysis (−log10-transformed P values from a moderated t test statistic vs log2-fold change of all genes) of gene-expression differences between LCH cells and LCs (E), mDC1s (F), and PDCs (G). Fold change and P value thresholds are indicated by dashed lines. Transcript highlighted by red circles is JAG2. Numbers in boxed areas indicate the number of transcripts. (H-I) Identification of LCH unique transcriptional profile: Venn diagram (Euler diagram) of significantly regulated (log-fold change > 2, P value adjusted for multiple testing < .05) genes comparing LCH with LCs, pDCs, and mDC1s. The relative sizes of circles indicate the relative sizes of gene sets. The overlapping areas of circles indicate the number of genes that are shared by 2 or more DC lineages. Among the regulated genes, 203 were up-regulated and 53 were down-regulated in all 3 DC lineages compared with LCH cells.

LCH cells form a distinct entity among indigenous human DCs. (A-B) LCH cell purification. Cell suspensions obtained from LCH biopsies carried out at the time of diagnosis contain a high number of LCH cells identified by CD1a expression and forward scatter properties. LCH cells were sorted to > 95% purity and reanalyzed for CD1a and Langerin expression. (C) Principal component analysis of LCH cells and 3 indigenous DC subsets. LCs and mDC1s cells are approximately equidistant from LCH cells, although in different axes (dimensions) of the gene space (ie, different gene sets separate LCH from LCs and mDCs). Each DC subset sample is presented by a triangle. LCs, mDC1s, and pDCs (n = 3 for each subset) were isolated from healthy subjects; LCH cells (n = 8) were isolated as shown in panel A. Because of superimpositions, not all symbols can be optically discerned in the displayed figure. (D) Similarity of LCH cells to indigenous DCs. Mean Pearson correlation coefficients of each replicate of LCs, mDC1s, pDCs, and LCH cells versus each replicate of LCH cells are depicted. Correlation coefficients are the highest among LCH samples, followed by mDC1s and LCs, indicating the highest similarity among LCH samples followed by virtually equal similarity of LCH cells to mDC1s and LCs. Results are shown as box plots displaying the medians and 25th and 75th percentiles as boxes and outliers as whiskers. (E-G) Identification of LCH transcripts selectively regulated compared with individual indigenous DC subsets. Volcano plot analysis (−log10-transformed P values from a moderated t test statistic vs log2-fold change of all genes) of gene-expression differences between LCH cells and LCs (E), mDC1s (F), and PDCs (G). Fold change and P value thresholds are indicated by dashed lines. Transcript highlighted by red circles is JAG2. Numbers in boxed areas indicate the number of transcripts. (H-I) Identification of LCH unique transcriptional profile: Venn diagram (Euler diagram) of significantly regulated (log-fold change > 2, P value adjusted for multiple testing < .05) genes comparing LCH with LCs, pDCs, and mDC1s. The relative sizes of circles indicate the relative sizes of gene sets. The overlapping areas of circles indicate the number of genes that are shared by 2 or more DC lineages. Among the regulated genes, 203 were up-regulated and 53 were down-regulated in all 3 DC lineages compared with LCH cells.

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