Fig. 5: Signaling among epithelial clusters in TME of MYC-driven prostate cancer.

A Cell communication plot of epithelial clusters from inferred ligand-receptor-transcription factor network analysis (Domino). Nodes represent individual clusters and are scaled based on ligand expression. Edges indicate signaling between two clusters and are weighted based on the strength of signaling. The edge color matches the cluster expressing the ligand. The ligands from the Luminal MYC 1 cluster is marked in yellow, while all other clusters are colored grey to highlight specific interactions from the Luminal MYC 1 cluster to all other epithelial clusters. B Heatmap showing which epithelial clusters express the top ligands targeting receptors expressed on the Reactive Basal cluster from inferred ligand-receptor pair interactions. C Heatmap showing the correlation of transcription factor activity scores (from SCENIC analysis) and receptor expression. Transcription factors were selected based on top activated scores in the Reactive Basal cluster. The receptors represented in this heatmap are known to bind to the top ligands targeting the Reactive Basal cluster. D Expression of downstream targets of the transcription factor interferon response factor 5 (IRF5) in epithelial clusters. E Plot showing NES of top 15 pathways by adjusted p-value. Statistics derived using fgsea implementation of a two-tailed GSEA, and the adjusted p-value from multiple hypothesis testing using Benjamini-Hochberg procedure. Comparisons include Luminal and Luminal MYC 1 clusters (top panel) and Basal and Reactive Basal clusters (bottom panel). Representative immunohistochemical staining in WT and Hi-Myc mouse prostate tissues of F CD3 to mark T cells (40 tissues) and G F4/80 to mark macrophages (36 tissues). In F, the 1x magnification scale bar indicates 1 mm and the 10x magnification scale bar indicates 100 μM. In G, the 1x magnification scale bar indicates 1 mm for WT and 2 mm for Hi-Myc. The 10x magnification scale bar indicates 200 μM. H Heatmaps of top 20 genes upregulated in the Luminal MYC 1 cluster at 6 months and downregulated at 10 months. Genes are grouped by associated gene sets from the GSEA Hallmark collection.