研究动态
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单细胞RNA测序揭示唾液腺恶性混合瘤内的肿瘤异质性:一项初步研究。

Single-cell RNA sequencing reveals tumor heterogeneity within salivary gland pleomorphic adenoma: A preliminary study.

发表日期:2023 Aug 07
作者: Xi-Qian Wang, Nian-Nian Zhong, Qi-Wen Man, Guang-Cai Xu, Si-Chen Yan, Li-Wei Peng, Yong-Gong Wang, Bing Liu, Lin-Lin Bu, Li Li
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

唾液腺多形性腺瘤是一种常见的唾液腺肿瘤,其组织学多样性显著。先前的研究已经证实基因重排和与细胞骨架重塑相关的肌上皮细胞在唾液腺多形性腺瘤的肿瘤发生中的参与。细胞骨架重塑对上皮间质转化(EMT)是肿瘤进展的关键过程所必需的。然而,关于肿瘤细胞和唾液腺多形性腺瘤中细胞骨架重塑的异质性尚未深入研究。 我们对来自两个唾液腺多形性腺瘤供体的27,810个细胞进行了单细胞RNA测序(scRNA-seq)分析。利用生物信息学工具评估了差异表达基因,细胞轨迹和细胞间通讯。免疫组织化学和双免疫荧光染色用于证明唾液腺多形性腺瘤组织中FOXC1和MYLK的表达。 我们的分析揭示了唾液腺多形性腺瘤肿瘤细胞中的五个不同亚型,表明病灶内部的异质性水平较高。与间质细胞密切相互作用的肿瘤细胞亚型3中高度富集了与细胞骨架重塑相关的基因。我们发现,肿瘤性FOXC1的表达与唾液腺多形性腺瘤的肿瘤细胞中MYLK的表达密切相关。 富含与细胞骨架重塑相关基因的肿瘤细胞在唾液腺多形性腺瘤的发展中发挥着关键作用,而FOXC1可能部分调控了这一过程。 © 2023 John Wiley & Sons A/S. 由John Wiley & Sons Ltd.发表。
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.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.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.Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.