A Single-cell Atlas of Human Prostate Spatially Resolved Using Spatial Transcriptomics

The prostate is an organ with significant spatial heterogeneity. In an effort to elucidate its complex structure and cellular composition, we constructed a comprehensive single-cell atlas of the adult human prostate. Our high-resolution mapping identified 253,381 single cells and 34,876 nuclei, which were categorized into 126 unique subpopulations. This work has revealed not only various novel cell types in the human prostate but also their spatial localization. Importantly, we discovered four distinct acini, two of which were tightly associated with ETS-fusion-negative prostate cancer. Based on integration of spatial, single-cell, and bulk-seq analyses, we propose that two specific luminal cell types could serve as the common origins of prostate cancer. We also found evidence suggesting that zone-specific fibroblasts may contribute to the observed heterogeneity of luminal cells. This atlas will serve as a valuable reference for studying prostate biology and diseases such as prostate cancer.