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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 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.

SUBMITTER: Chai C 

PROVIDER: S-EPMC10817929 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

Chai Chaochao C   Liang Langchao L   Mikkelsen Nanna S NS   Wang Wei W   Zhao Wandong W   Sun Chengcheng C   Bak Rasmus O RO   Li Hanbo H   Lin Lin L   Wang Fei F   Luo Yonglun Y  

Communications biology 20240126 1


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 epi  ...[more]

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