Fig. 5.

Meta-analysis of scRNA-seq datasets from human prostate adenocarcinoma reveals disease evolution of luminal acinar cells. A PHATE plot of LumAcinar populations from 2 normal prostates [13], 3 prostates with BPH [7], and 46 prostates with PCa from Memorial Sloan Kettering Cancer Center [6], University of California, San Francisco [14], Massachusetts General Hospital [15], Peking University Third Hospital [16], and Shanghai Changhai Hospital [17]. Clustering of the aggregated data reveals that LumAcinar cells show the greatest variation, as LumAcinar cells from the normal and BPH prostates occupy 1 cluster each (normal and hyperplasia, respectively), while cells in the PCa samples subdivide into 4 major subpopulations (intermediate, ERG-positive, AR-positive, and AR-low). The PHATE plot splits these PCa subpopulations along two major branches. B Dot plot of cell type, PCa, subpopulation-defining, and other relevant genes indicates that AR signaling is a major differentiating factor across the two branches. C Pseudotime analysis of the cells in A suggests a normal or intermediate origin for both branches in PCa. This also suggests progression through hyperplasia to PCa in some cells. D Heatmap comparing the total gene expression profiles of the LumAcinar subpopulations in A to all normal epithelial populations. The AR-low branch has a notable shift toward PrU and LumDuctal marker expression. Wasserstein distance is used as a metric, and darker red indicates greater transcriptomic similarity