Fig. 7: Activin A signals between spatially-connected infiltrative tumor cells and associated CAFs.

a Average expression level of the signature resulting from Activin A exposure in the fibroblast subpopulations of the scRNA-seq dataset, represented as a color scale overlaid on the UMAP plot (left panel) and as violin plots per ranked cluster (middle panel). Right panel shows the heatmap of average expression level of genes present in the signature in ranked clusters of the fibroblast subpopulations. b Correlation analysis between tumor INHBA and adjacent stromal FN1 relative intensities in nodular (N = 4) and infiltrative (N = 8) BCCs (n ≥ 10 regions/sample). R coefficient and p value were calculated by the Spearman correlation test and a two-sided statistical significance test, respectively. c Representative scan images of nodular and infiltrative BCC sections stained with DAPI (blue), INHBA (red), and FN1 (green) probes for RNA FISH. Upper, intermediate and lower zoom areas show tumor-stroma interface with distinct Nodular, Low, and High infiltrative morphologies respectively. Dotted lines highlight the tumor-stroma interface. Scale bars indicate 200 μm (main panels) and 20 μm (zoom panels). d Summary scheme depicting the continuum of tumor infiltrative properties, with a zoom on the cellular and molecular interactions identified within the invasive niche. Image designed with Servier Medical Art (smart.servier.com). scRNA-seq single-cell RNA sequencing, huBCC human basal cell carcinoma, UMAP uniform manifold approximation and projection, FC fibroblast cluster, BCC basal cell carcinoma, ECM extracellular matrix. Source data for b are provided as a Source data file.