Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
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.
Commun Biol. 2020 Dec 16;3(1):778. doi: 10.1038/s42003-020-01476-1.
Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.
神经内分泌前列腺癌是前列腺肿瘤中侵袭性最强的亚型之一。尽管在理解神经内分泌前列腺癌的发生发展方面已经取得了很大进展，但与人类前列腺癌中神经内分泌分化相关的细胞结构仍不完全清楚。在这里，我们使用单细胞 RNA 测序对 6 例去势抵抗性前列腺癌的针吸活检样本中的 21292 个细胞的转录组进行了分析。我们的分析表明，所有神经内分泌肿瘤细胞均表现出腔上皮样表型。特别是，谱系轨迹分析表明，局灶性神经内分泌分化仅源自腔上皮样恶性细胞，而不是基底细胞。进一步的组织微阵列分析验证了神经内分泌细胞的腔上皮样表型的普遍性。此外，我们还揭示了与神经内分泌分化相关的基因特征，这些特征可能有助于我们进一步探索导致神经内分泌前列腺癌的其他内在分子机制。总之，我们的单细胞研究为人类前列腺癌中神经内分泌转分化的细胞状态提供了直接证据。
