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.

前列腺干/祖细胞的鉴定和前列腺上皮细胞谱系层次的表征对于了解前列腺癌的发生至关重要。在这里，我们对来自小鼠前列腺的 35,129 个细胞进行了表征，并鉴定了一种独特的管腔细胞类型（称为 C 型管腔细胞 (Luminal-C)），以Tacstd2、Ck4和Psca表达为标志。位于远端前列腺内陷尖端的 Luminal-C 细胞（称为 Dist-Luminal-C）表现出更大的体外类器官形成和体内前列腺上皮导管再生能力。Luminal-C 细胞的谱系追踪表明，Dist-Luminal-C 细胞通过自我更新和分化重建远端前列腺管腔谱系。Dist-Luminal-C 细胞中Pten的缺失导致前列腺上皮内瘤变。我们进一步表征了 11,374 个人类前列腺细胞，并证实了 h-Luminal-C 细胞的存在。我们的研究提供了对前列腺谱系层次结构的深入了解，将 Dist-Luminal-C 细胞鉴定为内陷尖端中的管腔祖细胞群，并提出了前列腺癌的潜在细胞起源之一。