Fig. 6: INHBA is preferentially expressed in the highly infiltrative tumor tips.

a Venn diagram showing the overlap between genes with a positive (>0.1) pseudotime autocorrelation index and known CAF activators (upper panel). Lower panel shows the average expression level per ranked cluster of the three overlapping genes, ordered by decreasing autocorrelation index, in tumor cell subpopulations of the scRNA-seq dataset. b Expression level of INHBA in the tumor cell subpopulations of the scRNA-seq dataset, represented as a color scale overlaid on the UMAP plot (upper left panel) and as violin plots per ranked cluster (lower panel). Expression level per cell of INHBA along the pseudotemporal trajectory of tumor cell subpopulations (upper right panel). c Bar graph representing the relative intensity of INHBA expression in tumor cells located at the tumor-stroma interface of nodular (N = 4) and infiltrative (N = 8) BCC samples (measured in n ≥ 15 regions/sample). Horizontal bars indicate the mean ± SD. p Value was calculated by unpaired two-sided Student’s t test. d Representative scan images of nodular and infiltrative BCC sections stained with DAPI (blue) and INHBA (red) probe 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 panel) and 50 μm (zoom panels). e Representative confocal images of Nodular and High infiltrative tumor-stroma interfaces stained with DAPI (blue), pan-cytokeratin antibody (panCK, green), and INHBA (red) probe for RNA FISH. Dotted lines highlight the tumor-stroma interface. Scale bars indicate 10 μm. CAF cancer-associated fibroblasts, TC tumor cluster, scRNA-seq single-cell RNA sequencing, huBCC human basal cell carcinoma, UMAP uniform manifold approximation and projection, BCC basal cell carcinoma. Source data for c are provided as a Source data file.