Fig. 4

KT2 cells are proximal tubule cells exposed to mutagens. a Cartoon representing a kidney nephron and the location of the different tumor samples included in the analyses (according to [27, 36]). A section of proximal tubule (PT) is enlarged to show the trafficking of water, solutes, and other compounds across the PT epithelium. b tSNE plot of the trinucleotide profile of somatic SNVs in healthy (n = 161) and tumor (n = 192) samples. The common progenitors (SAT, VAT, SkM, and blood) and kidney-derived healthy and tumor genomes are highlighted with specific colors, while all other samples are shown in gray. c FACS analysis of the kidney progenitor markers CD133 and CD24 in selected KT1 and KT2 clones (n = 4). The average percentage of double- or single (CD24)-positive cells per clone is shown. d Heatmap showing the relative expression of markers of undifferentiated and differentiated kidney cells in single clones (subdivided in 11 categories described in the legend on the right) from either the KT1 (n = 4) or the KT2 (n = 2) group, tested by qPCR. Human embryonic stem cells (ESC bulk) and skin fibroblasts (SkFB bulk) were included as negative controls, together with a VAT clone. RNA extracted from a fresh kidney biopsy was included as positive control. The same KT1 clone is marked with an arrow in b and d, to highlight its intermediate KT1/KT2 phenotype at both somatic mutation (b) and gene expression (d) levels. KT1 and KT2, healthy kidney-tubule-derived cells; KIRC, clear cell renal cell carcinoma; KIRP, papillary renal cell carcinoma; KICH, chromophobe renal cell carcinoma; PT, proximal tubule; DT, distal tubule; S1, first segment of PT, convoluted; S3, last segment of PT, straight