Fig. 2. CDH12+ tumor population resembles characteristics of early undifferentiated urothelial cells and correlates with poor clinical outcome.

a UMAP of 12,819 uroepithelial nuclei obtained from histologically normal bladder and colored by unsupervised clustering. b Uroepithelial differentiation-related marker gene expression. c RNA velocity latent time trajectory in healthy bladder epithelial nuclei from a representative patient. d RNA velocity-based latent time of the nuclei shown in c. e Epithelial population density (top) and heatmap of uroepithelial marker gene expression (bottom) in nuclei from d ordered by increasing latent time. f Epithelial population distribution across latent time for all normal samples combined (top row) or MIBC samples based on normal nearest neighbor analysis (middle row). Normal samples were combined by collating the latent times from velocity analyses performed on each of the 4 samples independently. Disease-specific survival of high-grade MIBC in TCGA stratified by gene signature scores derived from MIBC nuclei in the latent time intervals demarcated by the dashed lines (bottom row, log-rank test between top and bottom quartiles N = 259).