1. Single-cell RNA sequencing of OSCC primary tumors and lymph nodes reveals distinct origin and phenotype of fibroblasts.
- Author
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Zhang Q, Ding L, Li J, Liu K, Xia C, Chen S, Huang X, Pu Y, Song Y, Hu Q, and Wang Y
- Subjects
- Humans, Lymphatic Metastasis, Cancer-Associated Fibroblasts metabolism, Cancer-Associated Fibroblasts pathology, Sequence Analysis, RNA methods, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck pathology, Squamous Cell Carcinoma of Head and Neck metabolism, Gene Expression Regulation, Neoplastic, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell metabolism, Male, Tumor Microenvironment, Transcriptome, Female, Mouth Neoplasms pathology, Mouth Neoplasms genetics, Mouth Neoplasms metabolism, Single-Cell Analysis methods, Lymph Nodes pathology, Lymph Nodes metabolism, Phenotype, Fibroblasts metabolism, Fibroblasts pathology
- Abstract
Desmoplasia in fibroblasts within metastatic lymph nodes (MLNs) serves as an indicator of extranodal extension (ENE), which led mortality in oral squamous cell carcinoma (OSCC). However, systematic studies on fibroblasts in MLNs are lacking. Therefore, this study characterized the differences in phenotype, function, and origin of fibroblasts between primary tumors (PTs) and lymph nodes (LNs) in OSCC. We generated single-cell maps of PTs and paired MLNs and draining LNs from three OSCC patients. The transcriptomic atlas, pseudotime analysis, intercellular communication networks and enrichment analysis of the single cells were characterized. Phenotype and function heterogeneity of fibroblast cells between PTs and MLNs were further verified in vitro. Among 44,052 fibroblasts, we identified two distinct subpopulations of cancer-associated myofibroblastic cells (mCAFs): RGS4
+ mCAF1 and COMP+ mCAF2. Notably, they exhibited distinct distributions, with mCAF1 predominantly localized in the PTs and mCAF2 in the MLNs. Moreover, pseudotime analysis revealed their distinct origins: mCAF1 originated from inherent normal myofibroblastic cells in the PT, whereas mCAF2 originated from fibroblastic reticular cells in the LNs. Further functional experiments using primary fibroblasts revealed that, compared to mCAF1, mCAF2 in MLNs exhibited weaker crosstalk with immune cells but enhanced extracellular matrix activity, which is closely linked to ENE formation in OSCC. Additionally, we identified two fibroblast subgroups in a transforming state, indicating a potential epithelial-mesenchymal transition. Our research offers profound insights into the heterogeneity of fibroblasts between the PT and MLN in OSCC, serving as an essential resource for future drug discovery endeavors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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