| Title | Single-Cell RNA-seq Reveals a Developmental Hierarchy Super-Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer |
| Authors | Ge, Guangzhe Han, Yang Zhang, Jianye Li, Xinxin Liu, Xiaodan Gong, Yanqing Lei, Zhentao Wang, Jie Zhu, Weijie Xu, Yangyang Peng, Yiji Deng, Jianhua Zhang, Bao Li, Xuesong Zhou, Liqun He, Huiying Ci, Weimin |
| Affiliation | Chinese Acad Sci, China Natl Ctr Bioinformat, Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing 100101, Peoples R China Peking Univ, Hosp 3, Sch Basic Med Sci, Dept Pathol,Hlth Sci Ctr, Beijing 100191, Peoples R China Peking Univ First Hosp, Dept Urol, Beijing 100034, Peoples R China Univ Chinese Acad Sci, Beijing 100049, Peoples R China Peking Univ, Inst Urol, Beijing 100034, Peoples R China Natl Urol Canc Ctr, Beijing 100034, Peoples R China Beijing Aerosp Ctr Hosp, Dept Urol, Beijing 100049, Peoples R China Peking Union Med Coll Hosp, Dept Urol, Beijing 100730, Peoples R China Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China |
| Keywords | TUMOR HETEROGENEITY METASTASIS STATISTICS INFERENCE |
| Issue Date | Mar-2022 |
| Publisher | ADVANCED SCIENCE |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/641547 |
| DOI | 10.1002/advs.202105530 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 第一医院 |
