State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Genet. 2020 Sep;52(9):908-918. doi: 10.1038/s41588-020-0642-1. Epub 2020 Aug 17.
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.
鉴定前列腺干细胞/祖细胞和描述前列腺上皮细胞谱系层级结构对于理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 35129 个细胞进行了表征，并鉴定出一种独特的腔细胞类型（称为 TACSTD2、CK4 和 PSA 表达的 C 型腔细胞（Luminal-C））。位于远端前列腺内陷尖端的 Luminal-C 细胞（称为 Dist-Luminal-C）具有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新构成远端前列腺腔系。在 Dist-Luminal-C 细胞中缺失 Pten 会导致前列腺上皮内瘤形成。我们进一步对 11374 个人类前列腺细胞进行了特征鉴定，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级结构的深入了解，鉴定出 Dist-Luminal-C 细胞作为内陷尖端的腔祖细胞群体，并提示了前列腺癌的潜在细胞起源之一。
