Distinct subtypes of CAFs are detected in human PDAC

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Distinct subtypes of CAFs are detected in human PDAC Distinct subtypes of CAFs are detected in human PDAC. A, Reclustering of CAFs in the human data set (cluster 7 from Fig. 1B) represented as a t-SNE plot. Distinct subtypes of CAFs are detected in human PDAC. A, Reclustering of CAFs in the human data set (cluster 7 from Fig. 1B) represented as a t-SNE plot. B, Heat map showing scaled normalized expression of discriminative marker genes between the two subclusters, with cells as columns and genes as rows. Color scheme represents Z-score distribution from −3 (blue) to 3 (dark orange). C–E, Violin plot of selected pan-CAF markers (C), iCAF markers (D), and myCAF markers (E) showing normalized expression in each of the subclusters. F, Network representation of selected differentially activated proteins between human iCAFs and myCAFs, as analyzed by VIPER. Proteins activated in iCAFs are shown in red; proteins activated in myCAFs are shown in blue. G, GSEA plot showing the enrichment score (ES) for a selected set of differentially activated proteins in iCAFs (shown in red) and myCAFs (shown in blue). H–I, VIPER plot showing the enrichment for the top 20 differentially activated signaling molecules (H) or transcription factors (I) between iCAFs and myCAFs. The top bar represents the ranked gene-expression signature between myCAFs and iCAFs. Regulatory target genes in each signaling molecule regulon or transcription factor regulon are represented by vertical lines projected along the gene-expression signature. Each vertical line represents the position of a regulatory target gene in the ranked signature between myCAFs and iCAFs. The colors of the lines indicate if the regulatory targets are positively (red) or negatively (blue) regulated by their corresponding signaling molecule or transcription factor, according to the ARACNe/VIPER inferred regulatory model. The two-column heat map on the right shows the inferred differential activity (Act) and the differential gene expression (Exp) of each regulon. The column on the left shows the P values associated with the enrichment of each regulon. Ela Elyada et al. Cancer Discov 2019;9:1102-1123 ©2019 by American Association for Cancer Research