Fig. 3: scRNA-seq reveals transcriptional changes, including amino acid transporter expression within the proximal tubular compartment in response to liver senescence.

a, A schematic of the scRNA-seq experiment. Three kidneys from control mice and three kidneys from ΔMdm2^Hep mice were dissociated, and droplet-based scRNA-seq was performed on them on a 10x Chromium chip. b, UMAP plots of all 24,215 cells (control and ΔMdm2^Hep). The cells are coloured on the basis of the broad clusters (left) or experimental group (right) (green, control; blue, ΔMdm2^Hep). c, UMAP plots showing the distribution of the cells that have a positive score for the p21 gene signature in the control (top) and the ΔMdm2^Hep (bottom) cells. The inset image is a representative kidney section from a ΔMdm2^Hep mouse stained for p21 by IHC with highlighted tubules (dashed lines). d, Pie charts showing the share of p21^high, TGFβ^high PTCs and JAK–STAT^high PTCs and mesenchymal cells in the control and ΔMdm2^Hep samples. Contingency was tested with the chi-square test (one-tailed). e, A bar chart showing the total number of cells with a positive score for the senescence transcriptional signature in the control and ΔMdm2^Hep samples (chi-square test (one-tailed)). f, A heat map showing the significantly differentially expressed Slc transporter genes in the PTC, DTC and LOH compartments. The gene IDs in the red frames are genes encoding transporters associated with amino acid transport. g, A schematic of the p21^KO experiment. Six Mdm2^E5/E6fl; p21^WT and six Mdm2^E5/E6fl; p21^KO mice were injected with AAV-Cre and culled 4 days later. h, The plasma levels of cystatin C in Mdm2^E5/E6fl; p21^WT and Mdm2^E5/E6fl; p21^KO mice 4 days post AAV injection. n = 6 for both groups; unpaired two-tailed t-test. The bars are the mean ± s.e.m., and the numbers on the graphs are P values. The source numerical data are available in Source data.