Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer.

Autor: Chai C; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 10049, China.; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China.; BGI Research, Shenzhen, 518083, China., Liang L; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 10049, China.; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China.; BGI Research, Shenzhen, 518083, China., Mikkelsen NS; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Wang W; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Zhao W; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 10049, China.; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China., Sun C; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 10049, China.; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China., Bak RO; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Li H; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China.; BGI Research, Shenzhen, 518083, China., Lin L; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark., Wang F; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China. wangfei@biomed.au.dk.; BGI Research, Shenzhen, 518083, China. wangfei@biomed.au.dk.; Department of Biomedicine, Aarhus University, Aarhus, Denmark. wangfei@biomed.au.dk., Luo Y; Lars Bolund Institute of Regenerative Medicine Qingdao-Europe Advanced Institute for LifeScience, BGI Research, Qingdao, 266555, China. alun@biomed.au.dk.; BGI Research, Shenzhen, 518083, China. alun@biomed.au.dk.; Department of Biomedicine, Aarhus University, Aarhus, Denmark. alun@biomed.au.dk.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. alun@biomed.au.dk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jan 26; Vol. 7 (1), pp. 131. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1038/s42003-024-05826-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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