Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression
Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression
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单细胞分析揭示了不同细胞类型中促进人类前列腺癌进展的转录组重塑
DOI：
10.1038/s41556-020-00613-6
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发表时间：
2021-01-01
影响因子：
21.3
通讯作者：
Ren, Shancheng
中科院分区：
文献类型：
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作者：
Chen, Sujun;Zhu, Guanghui;Ren, Shancheng
前列腺癌表现出显着的临床异质性，表现为空间和克隆基因组多样性。相比之下，前列腺肿瘤的转录组异质性知之甚少。在这里，我们分析了来自13个前列腺肿瘤的36，424个单细胞的转录组，并确定了疾病侵袭性的上皮细胞。肿瘤微环境（TME）显示多个进展相关转录组学程序的激活。值得注意的是，我们观察到混杂的KLK 3表达，并验证了癌细胞改变T细胞转录组的能力。原发肿瘤和两个匹配的淋巴结的分析提供了KLK 3异位表达与微转移相关的证据。细胞之间存在着密切的细胞间通讯。我们确定了一个内皮细胞亚群窝藏积极沟通（激活内皮细胞，aEC）与肿瘤细胞。结合另外11个样本的测序，我们发现aEC在去势抵抗性前列腺癌中富集，并促进癌细胞侵袭。最后，我们创建了一个用户友好的Web界面，供用户探索测序数据。
Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuousKLK3expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence thatKLK3ectopic expression is associated with micrometastases. Close cell–cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.