Figure 5 from Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type–Specific and Time-Resolved Responses to <i>Vhl</i> Inactivation in the Kidney
Kurlekar S., Lima JDCC., Li R., Lombardi O., Masson N., Barros AB., Pontecorvi V., Mole DR., Pugh CW., Adam J., Ratcliffe PJ.
<p><i>Vhl</i>-null cells specifically undergo time-dependent alterations in gene expression. <b>A,</b> 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>B,</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. <b>C,</b> Scatter plot depicting frequency of expression in tdTomato-positive cells from KO mice at the late time point against log<sub>2</sub>-fold change (log<sub>2</sub>FC) 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. <b>D,</b> Gene set enrichment plots depicting upregulation of genes regulated early after <i>Vhl</i> inactivation (left) or genes known to be HIF targets (right) in <i>Vhl</i>-null cells at the late versus early time points. NES, normalized enrichment score. <i>P</i> value adjusted by Bonferroni correction for multiple testing. <b>E,</b> 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. <b>F,</b> 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. <b>G,</b> Representative CD45 IHC on kidneys from Control (<i>n</i> = 1F, 4M) and KO (<i>n</i> = 6M) mice harvested at the late time point. Scale bar, 50 μm. Magnification, ×40. <b>A–F</b>, scRNA-seq data shown for <i>n</i> = 3F, 1M mice for Control early and Control late samples; <i>n</i> = 2F, 2M mice for KO early and KO late samples.</p>