Identification of a Zeb1 expressing basal stem cell subpopulation in the prostate
Identification of a Zeb1 expressing basal stem cell subpopulation in the prostate
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前列腺中表达 Zeb1 的基础干细胞亚群的鉴定
DOI：
10.1038/s41467-020-14296-y
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发表时间：
2020-02-05
影响因子：
16.6
通讯作者：
Zhu, Helen He
中科院分区：
文献类型：
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作者：
Wang, Xue;Xu, Haibo;Zhu, Helen He
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库。然而，基底细胞是异质性的，并且基底细胞内的干细胞亚群尚未得到很好的阐明。在这里，我们发现，核心上皮间质转化（EMT）诱导剂Zeb1在前列腺基底细胞亚群中表达。Zeb1（+）前列腺上皮细胞是多能性前列腺基底干细胞（PBSC），能够自我更新并在单细胞水平产生功能性前列腺腺体结构。基因消融研究揭示了Zeb1在前列腺基底细胞发育中不可或缺的作用。利用对超过9000个小鼠前列腺基底细胞的无偏单细胞转录组学分析，我们证实了Zeb1（+）基底细胞亚群的存在。此外，Zeb1（+）上皮细胞可以在小鼠和人前列腺肿瘤中检测到。PBSC及其转录组谱的鉴定对于促进我们对前列腺发育和肿瘤发生的理解至关重要。
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.