【文献速递】-Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contr...

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 promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic 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.
前列腺癌表现出显著的临床异质性，表现为空间和克隆基因组的多样性。相比之下，对前列腺肿瘤转录组的异质性了解甚少。在这里，我们对13个前列腺肿瘤的36424个单个细胞的转录组进行了分析，并确定了疾病侵袭性的上皮细胞。肿瘤微环境(TME)显示了多个进展相关的转录组程序的激活。值得注意的是，我们观察到了KLK3的混杂表达，并验证了癌细胞改变t细胞转录组的能力。对一个原发肿瘤和两个匹配淋巴结的分析表明，KLK3异位表达与微转移有关。细胞间存在着细胞间的通信。我们发现了一个内皮亚群，它与肿瘤细胞有活跃的通信(激活内皮细胞，aECs)。通过对另外11个样本的测序，我们发现aECs在抗去势前列腺癌中富集，并促进癌细胞侵袭。最后，我们为用户创建了一个友好的web界面来探索排序数据。

https://www.nature.com/articles/s41556-020-00613-6?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=JRCN_1_DD01_CN_NatureRJ_article_paid_XMOL