背景:唾液腺多形性腺瘤(SPA)是一种常见的唾液腺肿瘤,表现出明显的组织学多样性。先前的研究表明基因重排和细胞骨架重塑相关的肌上皮细胞参与SPA肿瘤发生。细胞骨架重塑是上皮-间质转化(EMT)所必需的,肿瘤进展的关键过程。然而,尚未广泛研究SPA中肿瘤细胞的异质性和细胞骨架重塑。
方法:对来自两个SPA供体的27个810细胞进行单细胞RNA测序(scRNA-seq)分析。生物信息学工具用于评估差异表达的基因,细胞轨迹,和细胞间通信。免疫组化和双重免疫荧光染色用于显示SPA组织中FOXC1和MYLK的表达。
结果:我们的分析揭示了SPA肿瘤细胞内的五种不同的细胞亚型,表明病变内异质性水平很高。细胞骨架重塑相关基因在肿瘤细胞亚型3中高度富集,与间充质细胞有密切的相互作用。我们发现在SPA肿瘤细胞中FOXC1的表达与MYLK的表达密切相关。
结论:富含细胞骨架重塑相关基因的肿瘤细胞在SPA发育中起着至关重要的作用,FOXC1可能会部分调控这一过程。
BACKGROUND: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated.
METHODS: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues.
RESULTS: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA.
CONCLUSIONS: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.