Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.

Guo, Wangxin; Li, Lin; He, Juan; Liu, Zhuang; Han, Ming; Li, Fei; Xia, Xinyi; Zhang, Xiaoyu; Zhu, Yao; Wei, Yu; Li, Yunguang; Aji, Rebiguli; Dai, Hao; Wei, Hui; Li, Chunfeng; Chen, Yu; Chen, Luonan; Gao, Dong

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.