Single‐cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer
Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet‐based single‐cell RNA sequenc...
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| Published in | International journal of cancer Vol. 149; no. 12; pp. 2099 - 2115 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken, USA
John Wiley & Sons, Inc
15.12.2021
Wiley Subscription Services, Inc |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet‐based single‐cell RNA sequencing (scRNA‐seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial‐mesenchymal transition (EMT) and mainly located at the tumor‐stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle‐invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single‐cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.
What's new?
Extensive heterogeneity in bladder cancer has inspired novel approaches to the investigation of underlying mechanisms, including genomic and phenotypic single‐cell analyses. In this single‐cell characterization of tumor cell heterogeneity in bladder cancer, basal‐like tumor cells were found to possess epithelial‐to‐mesenchymal transition (EMT) features, including enrichment of EMT‐associated genes. Basal‐like cells further exhibited a potential to generate luminal daughter cells, making them possible precursors for local invasion. In addition, aggressive cells with upregulation of stemness‐related genes were observed in a muscle‐invasive T3‐stage tumor. The findings suggest that invasive cell subsets within bladder cancers may serve a significant role in disease progression. |
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| AbstractList | Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet‐based single‐cell RNA sequencing (scRNA‐seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial‐mesenchymal transition (EMT) and mainly located at the tumor‐stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle‐invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single‐cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.
What's new?
Extensive heterogeneity in bladder cancer has inspired novel approaches to the investigation of underlying mechanisms, including genomic and phenotypic single‐cell analyses. In this single‐cell characterization of tumor cell heterogeneity in bladder cancer, basal‐like tumor cells were found to possess epithelial‐to‐mesenchymal transition (EMT) features, including enrichment of EMT‐associated genes. Basal‐like cells further exhibited a potential to generate luminal daughter cells, making them possible precursors for local invasion. In addition, aggressive cells with upregulation of stemness‐related genes were observed in a muscle‐invasive T3‐stage tumor. The findings suggest that invasive cell subsets within bladder cancers may serve a significant role in disease progression. Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression. Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet‐based single‐cell RNA sequencing (scRNA‐seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial‐mesenchymal transition (EMT) and mainly located at the tumor‐stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle‐invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single‐cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression. Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet‐based single‐cell RNA sequencing (scRNA‐seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial‐mesenchymal transition (EMT) and mainly located at the tumor‐stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle‐invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single‐cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression. What's new? Extensive heterogeneity in bladder cancer has inspired novel approaches to the investigation of underlying mechanisms, including genomic and phenotypic single‐cell analyses. In this single‐cell characterization of tumor cell heterogeneity in bladder cancer, basal‐like tumor cells were found to possess epithelial‐to‐mesenchymal transition (EMT) features, including enrichment of EMT‐associated genes. Basal‐like cells further exhibited a potential to generate luminal daughter cells, making them possible precursors for local invasion. In addition, aggressive cells with upregulation of stemness‐related genes were observed in a muscle‐invasive T3‐stage tumor. The findings suggest that invasive cell subsets within bladder cancers may serve a significant role in disease progression. |
| Author | Ji, Zhongzhong Zhang, Lianhua Luo, Wenqin Zhang, Man Song, Weichen Lai, Huadong Liu, Qiang Wang, Jia Liu, Mengyao Lin, Guan Ning Yang, Guoliang Cheng, Xiaomu Bo, Juanjie Miao, Juju Gao, Wei‐Qiang |
| Author_xml | – sequence: 1 givenname: Huadong surname: Lai fullname: Lai, Huadong organization: Shanghai Jiao Tong University – sequence: 2 givenname: Xiaomu surname: Cheng fullname: Cheng, Xiaomu organization: Shanghai Jiao Tong University – sequence: 3 givenname: Qiang surname: Liu fullname: Liu, Qiang organization: Shanghai Jiao Tong University – sequence: 4 givenname: Wenqin surname: Luo fullname: Luo, Wenqin organization: Shanghai Jiao Tong University – sequence: 5 givenname: Mengyao surname: Liu fullname: Liu, Mengyao organization: Shanghai Jiao Tong University – sequence: 6 givenname: Man surname: Zhang fullname: Zhang, Man organization: Shanghai Jiao Tong University – sequence: 7 givenname: Juju surname: Miao fullname: Miao, Juju organization: Shanghai Jiao Tong University – sequence: 8 givenname: Zhongzhong surname: Ji fullname: Ji, Zhongzhong organization: Shanghai Jiao Tong University – sequence: 9 givenname: Guan Ning surname: Lin fullname: Lin, Guan Ning organization: Shanghai Jiao Tong University – sequence: 10 givenname: Weichen surname: Song fullname: Song, Weichen organization: Shanghai Jiao Tong University – sequence: 11 givenname: Lianhua surname: Zhang fullname: Zhang, Lianhua organization: Shanghai Jiao Tong University – sequence: 12 givenname: Juanjie surname: Bo fullname: Bo, Juanjie organization: Shanghai Jiao Tong University – sequence: 13 givenname: Guoliang surname: Yang fullname: Yang, Guoliang email: yangguoliang@renji.com organization: Shanghai Jiao Tong University – sequence: 14 givenname: Jia surname: Wang fullname: Wang, Jia email: wang_jia@fudan.edu.cn organization: Shanghai Jiao Tong University – sequence: 15 givenname: Wei‐Qiang orcidid: 0000-0002-1989-4927 surname: Gao fullname: Gao, Wei‐Qiang email: gao.weiqiang@sjtu.edu.cn organization: Shanghai Jiao Tong University |
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| Notes | Funding information Ministry of Science and Technology of the People's Republic of China, Grant/Award Number: 2017YFA0102900; National Natural Science Foundation of China, Grant/Award Numbers: 81872406, 81630073, 81902561; 111 Project, Grant/Award Number: B21024; Science and Technology Commission of Shanghai Municipality, Grant/Award Number: 20JC1417600; KC Wong Foundation, Shanghai Health Bureau, Grant/Award Number: 20164Y0124; Shanghai Pujiang Program, Grant/Award Number: 20PJ1409800; The Shanghai Young Eastern Scholar Funds, Grant/Award Number: QD2018021; Peak Disciplines(Type IV) of Institutions of Higher Learning in Shanghai; Incubating Program for clinical Research, Innovation of Renji Hospital Shanghai Jiao Tong University School of Medicine, Grant/Award Number: PYII‐17‐010 Huadong Lai, Xiaomu Cheng contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 |
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| SubjectTerms | Basal cells Bladder cancer Cancer Epithelial cells intratumoral heterogeneity Invasiveness Lamina propria Medical research Mesenchyme Phenotypes single‐cell RNA sequencing Sox9 protein Stem cells Transcription Tumor cells tumor cells communication tumor invasion |
| Title | Single‐cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer |
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