Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer
Autor: | Jiahua Pan, Yu-Xiang Fang, Wenqin Luo, Helen He Zhu, Zhongzhong Ji, Wei-Qiang Gao, Chee Wai Chua, Jinming Wang, Wei Xue, Xiaomu Cheng, Liancheng Fan, Baijun Dong, Yinjie Zhu, Man Zhang, Yanqing Wang, Juju Miao, Huadong Lai, Jia Wang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Epithelial-Mesenchymal Transition QH301-705.5 Biopsy Medicine (miscellaneous) Biology Neuroendocrine differentiation Article General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Prostate cancer 0302 clinical medicine Neuroendocrine Cells Single-cell analysis Prostate Cell Line Tumor medicine Humans Epithelial–mesenchymal transition Biology (General) Aged Aged 80 and over Gene Expression Profiling Transdifferentiation Computational Biology Prostatic Neoplasms Cancer medicine.disease Phenotype Computational biology and bioinformatics Carcinoma Neuroendocrine Gene Expression Regulation Neoplastic Gene expression profiling Neuroendocrine cancer 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Single-Cell Analysis General Agricultural and Biological Sciences |
Zdroj: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-15 (2020) |
ISSN: | 2399-3642 |
Popis: | 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. Using single-cell RNA sequencing, Dong, Miao, Wang et al. profile the transcriptomes of 21,292 cells from biopsies of 6 castration-resistant prostate cancers. They find that all neuroendocrine tumor cells display a luminal-like epithelial phenotype, providing insights into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer. |
Databáze: | OpenAIRE |
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