Vhl-null cells specifically undergo time-dependent alterations in gene expression. A, Density plot depicting UMAP distribution of tdTomato-positive cells from kidneys of Control and KO mice harvested at the early or late time points. B, Left, UMAP plot depicting tdTomato-positive cells from Control and KO mice harvested at the early and late time points colored by UMAP cluster. Right, proportion of cells from each condition belonging to any cluster. C, Scatter plot depicting frequency of expression in tdTomato-positive cells from KO mice at the late time point against log2-fold change (log2FC) between cells from KO mice at the late versus early time points for all genes. Orange, significantly regulated genes. Genes explicitly mentioned in the main text are labeled. D, Gene set enrichment plots depicting upregulation of genes regulated early after Vhl inactivation (left) or genes known to be HIF targets (right) in Vhl-null cells at the late versus early time points. NES, normalized enrichment score. P value adjusted by Bonferroni correction for multiple testing. E, UMAP plot depicting “PT like” cells among tdTomato-positive cells from Control and KO mice harvested at the early and late time points. Black, PT-like cells. F, Proportion of cells inferred to be “PT like” within tdTomato-positive (top) or tdTomato-negative (bottom) cells across conditions. Median and interquartile range plotted. Pairwise comparisons tested by one-way ANOVA with Holm–Šídák correction. G, Representative CD45 IHC on kidneys from Control (n = 1F, 4M) and KO (n = 6M) mice harvested at the late time point. Scale bar, 50 μm. Magnification, ×40. A–F, scRNA-seq data shown for n = 3F, 1M mice for Control early and Control late samples; n = 2F, 2M mice for KO early and KO late samples.