State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.
Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
Nat Commun. 2020 Feb 5;11(1):706. doi: 10.1038/s41467-020-14296-y.
The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation. The Zeb1 prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single-cell transcriptomic analysis of over 9000 mouse prostate basal cells, we confirm the existence of the Zeb1 basal cell subset. Moreover, Zeb1 epithelial cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.
许多上皮组织中的基底细胞区室通常被认为是干细胞的重要来源。然而，基底细胞是异质的，基底细胞内的干细胞亚群尚未得到充分阐明。在这里，我们发现核心上皮-间充质转化（EMT）诱导因子 Zeb1 在上皮细胞中的表达在前列腺基底细胞亚群中。Zeb1 前列腺上皮细胞是多能性前列腺基底干细胞（PBSC），能够在单细胞水平上自我更新并产生功能性前列腺腺结构。基因敲除研究揭示了 Zeb1 在前列腺基底细胞发育中的不可或缺的作用。利用超过 9000 个小鼠前列腺基底细胞的无偏单细胞转录组分析，我们证实了 Zeb1 基底细胞亚群的存在。此外，Zeb1 上皮细胞可在小鼠和人前列腺肿瘤中检测到。鉴定 PBSC 及其转录组图谱对于深入了解前列腺发育和肿瘤发生至关重要。
