SOX2 and neoplasm: To further exclude the possibility that Cluster 13 is a progenitor cell state rather than a derivative tumor cell state, we generated a nine-gene bladder stem cell signature (PROM1 (CD133), POU5F1 (Oct4), SOX2, ALDH1A1, SOX4, EZH2, YAP1, CD44, and KRT14) based on previous studies in bladder cancer stem cells34–36; we found no significant enrichment of this signature in Cluster 13 cells (Supplementary Fig. 8).