Fig. 3: Analysis of EC and fibroblast cells in PCPG and NAM tissues.

a Supervised classification and enumeration of fibroblast and EC cells in PCPG. Proportions of fibroblasts and ECs within each sample (top panel) and the functional subtypes that make up each major cell type (bottom panels). b Dot plot of the DE cell type/pathway marker genes of interest expressed in each functional cell subset. Top ranked DE genes contrasting fibroblasts and ECs from tumor and NAM tissues, respectively, in addition to pro-angiogenesis genes EPAS1, VEGFA and the anti-angiogenesis genes ISM1, HIF3A found DE between NEO and normal chromaffin cells from NAM tissues. Dot plot shows expression from nuclei combined from multiple tumors according to cell type as well as NAM tissues. Chromaffin cells shown are from NAM tissues only. c, d UMAP reclustering of c fibroblasts (nCells = 2901) and d ECs (nCells = 5430) from all tumor and normal samples analyzed by snRNA-seq. Nuclei are colored according to cell subtype classification. e Spearman-rank correlation for HIF-related genes in NEO cells. f Pseudo-bulk expression across PCPG samples (NEO cells from tumors combined for genotype/subtype analysis) for the genes described in (e). g Bulk-tissue gene-expression of angiogenesis gene markers as well as EPAS1 and VEGFA within PCPG subtypes (nSamples = 645) (The lower and upper hinges of each boxplot correspond to the first and third quartiles, respectively, and the median value is marked. The whiskers extend to the largest and smallest value not greater than 1.5 times the interquartile range above or below the upper and lower hinges, respectively. Values beyond the whisker extents are deemed outliers and are plotted individually). WT (NAM): Wild type normal adrenal medulla. Differential gene expression was determined by limma using empirical Bayes moderated t-statistics, and adjusted for FDR with Benjamini-Hochberg (BH) correction.