Extended Data Fig. 6: Regulation of redox balance by TFE3 fusions in tRCC.
a, Ratio of GSH to GSSG levels as measured by untargeted metabolomics in three ccRCC cell lines (786-O, A498, RCC4) vs. three tRCC cell lines (UOK109, FU-UR-1, s-TFE). Data are shown as mean -+ s.d for each group of cell lines. for n = 5 biological replicates per cell line. b, Profile plot showing TFE3 fusion ChIP-Seq signal at glutathione metabolism and pentose phosphate pathway (PPP) genes. c, Schematic of glutathione metabolism and PPP, annotated with genes that are ASPL-TFE3 targets as determined by ChIP-Seq in s-TFE cells (orange boxes). In the schematic, enzymes are in black text, metabolites are in grey text. d, Heatmap showing the change in expression of glutathione metabolism and PPP-related genes following ASPSCR1-TFE3 knockout in s-TFE cells or knockdown in FU-UR-1 cells. e, Change in levels of glutathione metabolism and PPP-related metabolites following ASPSCR1-TFE3 knockout in s-TFE cells. For each metabolite, fold change was normalized to control sgRNA condition. Data are shown as mean and individual replicates for n = 5 biological replicates per cell line. f, Intracellular ROS level in ccRCC and tRCC cell lines. Quantification of intracellular ROS levels via CM-H2DCFDA indicator in tRCC (n = 3, UOK109, FU-UR-1, s-TFE) and ccRCC cell lines (n = 5, 786-O, Caki-1, KRMC-1, RCC4, A498). Points shown are mean across replicates each cell line and horizontal line represents mean for each group of cell lines. g, Intracellular ROS levels (measured by CM-H2DCFDA indicator) after TFE3 knockout in ccRCC cell line (786-O) and tRCC cell lines (UOK109, FU-UR-1). For (a), and (e-f), statistical significance was determined by two-sided Mann–Whitney test.
