Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer
Abstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evol...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202105530 |
| _version_ | 1818551482382811136 |
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| author | Guangzhe Ge Yang Han Jianye Zhang Xinxin Li Xiaodan Liu Yanqing Gong Zhentao Lei Jie Wang Weijie Zhu Yangyang Xu Yiji Peng Jianhua Deng Bao Zhang Xuesong Li Liqun Zhou Huiying He Weimin Ci |
| author_facet | Guangzhe Ge Yang Han Jianye Zhang Xinxin Li Xiaodan Liu Yanqing Gong Zhentao Lei Jie Wang Weijie Zhu Yangyang Xu Yiji Peng Jianhua Deng Bao Zhang Xuesong Li Liqun Zhou Huiying He Weimin Ci |
| author_sort | Guangzhe Ge |
| collection | DOAJ |
| description | Abstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single‐cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT‐like (subtype 0), luminal A‐like (subtype 1), luminal B/C‐like (subtype 2), and basal‐like (subtype 3). These subtypes are hierarchically organized into stem cell‐like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis. |
| first_indexed | 2024-12-12T09:00:29Z |
| format | Article |
| id | doaj.art-01377a71593447d99e493ff59cc8a27a |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-12T09:00:29Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-01377a71593447d99e493ff59cc8a27a2022-12-22T00:29:50ZengWileyAdvanced Science2198-38442022-05-01915n/an/a10.1002/advs.202105530Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate CancerGuangzhe Ge0Yang Han1Jianye Zhang2Xinxin Li3Xiaodan Liu4Yanqing Gong5Zhentao Lei6Jie Wang7Weijie Zhu8Yangyang Xu9Yiji Peng10Jianhua Deng11Bao Zhang12Xuesong Li13Liqun Zhou14Huiying He15Weimin Ci16Key Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics China National Center for Bioinformation Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics China National Center for Bioinformation Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics China National Center for Bioinformation Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics China National Center for Bioinformation Chinese Academy of Sciences Beijing 100101 ChinaDepartment of Pathology School of Basic Medical Sciences Third Hospital Peking University Health Science Center Beijing 100191 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Beijing Aerospace Center Hospital Beijing 100049 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Peking Union Medical College Hospital Beijing 100730 ChinaDepartment of Urology Beijing Aerospace Center Hospital Beijing 100049 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Urology Peking University First Hospital Beijing 100034 ChinaDepartment of Pathology School of Basic Medical Sciences Third Hospital Peking University Health Science Center Beijing 100191 ChinaKey Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics China National Center for Bioinformation Chinese Academy of Sciences Beijing 100101 ChinaAbstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single‐cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT‐like (subtype 0), luminal A‐like (subtype 1), luminal B/C‐like (subtype 2), and basal‐like (subtype 3). These subtypes are hierarchically organized into stem cell‐like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis.https://doi.org/10.1002/advs.202105530cellular ecosystemepithelial‐to‐mesenchymal transitionprostate cancersubtypetranscriptional heterogeneitytumor subclone |
| spellingShingle | Guangzhe Ge Yang Han Jianye Zhang Xinxin Li Xiaodan Liu Yanqing Gong Zhentao Lei Jie Wang Weijie Zhu Yangyang Xu Yiji Peng Jianhua Deng Bao Zhang Xuesong Li Liqun Zhou Huiying He Weimin Ci Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer Advanced Science cellular ecosystem epithelial‐to‐mesenchymal transition prostate cancer subtype transcriptional heterogeneity tumor subclone |
| title | Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| title_full | Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| title_fullStr | Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| title_full_unstemmed | Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| title_short | Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| title_sort | single cell rna seq reveals a developmental hierarchy super imposed over subclonal evolution in the cellular ecosystem of prostate cancer |
| topic | cellular ecosystem epithelial‐to‐mesenchymal transition prostate cancer subtype transcriptional heterogeneity tumor subclone |
| url | https://doi.org/10.1002/advs.202105530 |
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