Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer
Abstract A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected fro...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-05826-1 |
| _version_ | 1827328997858476032 |
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| author | Chaochao Chai Langchao Liang Nanna S. Mikkelsen Wei Wang Wandong Zhao Chengcheng Sun Rasmus O. Bak Hanbo Li Lin Lin Fei Wang Yonglun Luo |
| author_facet | Chaochao Chai Langchao Liang Nanna S. Mikkelsen Wei Wang Wandong Zhao Chengcheng Sun Rasmus O. Bak Hanbo Li Lin Lin Fei Wang Yonglun Luo |
| author_sort | Chaochao Chai |
| collection | DOAJ |
| description | Abstract A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC. |
| first_indexed | 2024-03-07T15:27:31Z |
| format | Article |
| id | doaj.art-23ff22a4c6ce4ede80656bf694d0bea8 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-07T15:27:31Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-23ff22a4c6ce4ede80656bf694d0bea82024-03-05T16:38:37ZengNature PortfolioCommunications Biology2399-36422024-01-017111510.1038/s42003-024-05826-1Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancerChaochao Chai0Langchao Liang1Nanna S. Mikkelsen2Wei Wang3Wandong Zhao4Chengcheng Sun5Rasmus O. Bak6Hanbo Li7Lin Lin8Fei Wang9Yonglun Luo10College of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesDepartment of Biomedicine, Aarhus UniversityDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCollege of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesDepartment of Biomedicine, Aarhus UniversityLars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI ResearchDepartment of Biomedicine, Aarhus UniversityLars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI ResearchLars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI ResearchAbstract A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC.https://doi.org/10.1038/s42003-024-05826-1 |
| spellingShingle | Chaochao Chai Langchao Liang Nanna S. Mikkelsen Wei Wang Wandong Zhao Chengcheng Sun Rasmus O. Bak Hanbo Li Lin Lin Fei Wang Yonglun Luo Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer Communications Biology |
| title | Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer |
| title_full | Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer |
| title_fullStr | Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer |
| title_full_unstemmed | Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer |
| title_short | Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer |
| title_sort | single cell transcriptome analysis of epithelial immune and stromal signatures and interactions in human ovarian cancer |
| url | https://doi.org/10.1038/s42003-024-05826-1 |
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