Fig. 3: Epithelial-to-mesenchymal transition in the tumor microenvironment.

a Zoom of UMAP embeddings of the cohorts’ long-read–gene-level data (Fig. 2a, middle column) highlighting tumor and stromal (mesothelial and fibroblast) cells, colored by biopsy tissue type (left) and EMT gene set signal (right). b Volcano plot of genes with APA in mesothelial cells. Genes have either a lengthened (red) or shortened (blue) 3’UTR in TME compared to distal mesothelial cells. Differentially lengthened or shortened genes targeted by miR-29 are colored in green. Genes with -log10(p-adjusted) >10 and |Fraction Change| >0.4 are annotated. APA statistical test is described in “Methods” (c) IGV view of 3’UTR raw coverage of COL1A2, COL6A1, COL3A1, and COL5A2 in tissue cell types. On the top left between brackets, the coverage range is displayed throughout each condition. In blue, Ensembl canonical 3’UTR, and for each gene, distal (d) and proximal (p) APA sites are annotated. d Log fold-change expression between TME and distal mesothelial cells of lengthened genes targeted (+, green, n = 9) or not targeted (−, red, n = 12) by miR-29, and shortened genes (blue, n = 19). Boxes display the first to third quartile with median as horizontal line, whiskers encompass 1.5 times the interquartile range, and data beyond that threshold is indicated as outliers. P values were calculated using a two-sided Student’s t-test between the fold-change means. e Cohort UMAP embedding long-read data—gene level, colored by gene set signal of ECM-related genes targeted by miR-29. f ScisorWiz representation of COL1A1 isoforms. Colored areas are exons, whitespace areas are intronic space, not drawn to scale, and each horizontal line represents a single read colored according to cell types. Dashed boxes highlight the use of the canonical 3’ UTR in TME fibroblasts and mesothelial cells, while distal mesothelial cells use an earlier 3’ exon termination.