Fig. 1: Single-cell RNA sequencing of treated (A-J) and (K-M) naive RMC tumours.

a UMAP plot of the aggregated treated tumour and normal adjacent tissue (NAT) representing the clusters identified by Seurat using a resolution of 1.12. PCT proximal convoluted tubule cells, PST1/2 proximal straight tubule cells 1 and 2, RMC renal medullary carcinoma cells, TAL1 thick ascending tubule cells of Henle’s loop, DCT distal convoluted tubule cells, CNT connecting tubule cells, CD collecting duct cells, CAF cancer-associated fibroblasts, MES mesangial cells, ED endothelial cells, RBC red blood cells, PEC parietal epithelial cells, POD podocytes, TAM1 tumour-associated macrophages. b UMAP projection of sample origin or selected gene signatures. c Dot-plots representing gene markers of each identified cluster in the RMC treated sample. Rectangles regroup clusters according to either mesenchymal or epithelial markers. d Clustifyr correlation between RMC cells and renal epithelial tubules transcriptomes. e Pseudo-bulk heatmap of 100 RMC-specific and 50 CAF-specific genes using CAF1, RMC and TAL1 clusters as a matrix. f UMAP representing RMC subclusters as identified by Seurat using a resolution of 1. g GSEA showing enriched “Hallmark gene sets” in RMC1 relative to RMC2 cell clusters. h Clustifyr correlation between RMC subclusters and renal epithelial tubules transcriptomes. i SWNE trajectory analysis of the treated RMC clusters using a set of selected markers per cluster and assuming TAL1 cells as origin. j Heatmap representation of a set of selected EMT genes in the 2 RMC subclusters. k UMAP plot of the naive tumour cell clusters as identified by Seurat. RMC3/4: Renal medullary carcinoma cells; TAL2/3: thick ascending tubule cells of Henle’s loop; NEU neutrophils, CAF2 cancer-associated fibroblasts, NK natural killers, TLC T-lymphocyte cells, TAM2/3 tumour-associated macrophages. l Dot-plots of selected gene markers of immune, epithelial and CAF cells. m UMAP projection of the bulk RMC and cytokeratin signatures.