Fig. 1: Cystine storage diverts differentiation towards growth and proliferation.

a Cystine levels in Ctns mouse kidneys; n = 6 animals in each experimental group. b Immunofluorescence and quantification of the Lamp1 mean fluorescence intensity (MFI) in the LTL⁺ PT segments of Ctns mouse kidneys, n = 164 Ctns^WT and n = 137 Ctns^KO PT segments from 3 biologically independent animals. c Confocal microscopy and quantification of the Cy5-tagged β-lactoglobulin MFI in the LTL⁺ PT segments of Ctns mouse kidneys, n = 356 Ctns^WT and n = 330 Ctns^KO PT segments from 3 biologically independent animals. d Quantification of LMW/Clara cell protein (CC16) levels in the urine samples of Ctns mice; n = 7 animals in each experimental group. e Volcano plot of genome-wide changes in PT segments of Ctns mouse kidneys. Red and green dots show the differentially expressed genes (DEGs; adjusted p value < 0.05; n = 3 animals in each experimental group). f GSEA of over- and under-represented biological pathways in the PT segments of Ctns^KO mouse kidneys. FDR q value was calculated from the enrichment pathway analysis in NetworkAnalyst. g Immunoblotting and quantification of the indicated proteins in the kidneys of Ctns mice; n = 3 animals in each experimental group. h Confocal microscopy of whole-kidney sections stained for Ccna2 (red), Lrp2 (blue), and PT marker (LTL, green); quantification of Ccna2⁺ nuclei and of Lrp2 MFI in the PT segments of Ctns mouse kidneys. For Ccna2⁺ nuclei: n = 31 Ctns^WT and n = 54 Ctns^KO PT segments from  3 biologically independent animals. For Lrp2 MFI: n = 60 Ctns^WT and n = 56 Ctns^KO PT segments from  3 biologically independent animals. i mRNA levels for the indicated genes in the kidneys of Ctns mice; n = 8 biologically independent animals. j Whole-kidney sections stained for PT apical marker (Aqp1, green) and PT basolateral marker (Laminin, red). Confocal microscopy and quantification of PT cell height in the kidneys of Ctns mouse; n = 90 PT segments from 3 biologically independent animals. Plots represent mean ± SEM. Statistics calculated by unpaired two-tailed Student’s t test. Dotted white squares contain images at high magnification. Nuclei counterstained with DAPI (grey). Scale bars are 50 μm in b, c, and h and 20 μm in j. Source data are provided as a Source Data file.