Fig. 7: Stromal reprogramming in the TME of MYC-driven prostate cancer.
From: Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer
A Immune clusters were subsetted from dorsal and lateral lobes of FVB/NJ mice from WT and Hi-Myc at 6 months and 10 months (n = 6,162 cells, 12 samples). A fibroblast subcluster enriched in Hi-Myc tissue expresses Timp1. B Scatter plots showing the proportion of select stromal cell populations significantly altered in Hi-Myc compared to WT. Each dot represents a sample (n = 12) colored by genotype and age. Bars represent the mean cell proportion of samples for each group. RAISIN’s cell proportions test used to statistically compare WT (n = 6) and Hi-Myc (n = 6) samples. The adjusted p-value is derived from a two-sided t-test and adjusted for multiple hypothesis testing using Benjamini-Hochberg. C Violin plot showing expression of Pdgfra, Timp1, and fibrosis-associated collagens (Col1a1, Col1a2, Col3a1, Col5a2) by genotype (WT and Hi-Myc) and age (6 months and 10 months) in fibroblast cells. D UMAP of human stromal cell clusters (n = 18,837 cells, 18 samples). Right panel shows the expression of the Hi-Myc Fibroblast Timp1 gene signature (TIMP1, MFAP5, SERPINA3, IGF1, SFRP1, MMP2, SERPINF1, COL1A1, COL5A2, COL3A1). E Scatter plot showing proportion of Macrophages Trem2 and Fibroblast Timp1 clusters for each sample with corresponding two-tailed Pearson correlation coefficient and p-value. F Inferred ligand-receptor-transcription factor network analysis (Domino) of epithelial, macrophage, and fibroblast clusters from FVB/NJ aggregated scRNA-seq data. Luminal MYC 1 cluster is marked in red, Macrophages Trem2 cluster is marked in yellow, Fibroblast Timp1 node is marked in black, and all other clusters are colored grey. G Heatmap showing which clusters express the top ligands targeting the Fibroblast Timp1 cluster. H Heatmap showing the correlation of transcription factor activity scores (derived from SCENIC) and receptor expression. Transcription factors were selected based on top activated scores in the Fibroblast Timp1 cluster. Receptors for TNF, PTPRC, CD72, OSM, and TGFB1 are shown.
