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[内皮细胞和成纤维细胞介导颈动脉体副神经节瘤的微环境调节网络]

[Endothelial cells and fibroblasts mediate the microenvironmental regulatory network of carotid body paraganglioma].

作者信息

Zhang Boya, Wang Shengming, Hu Yibing, Luo Chunyu, Li Shiyuan, Lou Zihan, Wang Jingjing, Chen Zhengnong, Yin Shankai

机构信息

Department of Otorhinolaryngology Head and Neck Surgery,Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,200233,China.

出版信息

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Sep;38(9):788-796. doi: 10.13201/j.issn.2096-7993.2024.09.003.

Abstract

To explore the gene expression characteristics of endothelial cells and fibroblasts in the microenvironment of -mutated carotid body tumors(-CBT), to fine the functional enrichment of each subcluster, and to further explore the network of cell-cell interactions in the microenvironment of -CBT. The bioinformatics analysis was used to download and reanalyze the single-nuclear RNA sequencing data of -CBT, mutated thoracic and abdominal paraganglioma(-ATPGL), -CBT, and normal adrenal medulla(NAM), to clarify the information of cell populations of the samples. We focused on exploring the gene expression profiles of endothelial cells and fibroblasts subclusters, and performed functional enrichment analysis based on Gene Ontology(GO) resources. CellChat was used to compare the cell-cell interactions networks of different clinical samples and predict significant signaling pathways in -CBT. A total of 7 cell populations were profiled. The main subtypes of endothelial cells in -CBT are arterial and venous endothelial cells, and the main subtypes of fibroblasts are myofibroblasts and pericytes. Compared to NAM, -CBT and -ATPGL, cell communication involving endothelial cells and fibroblasts in -CBT is more abundant, with significant enrichment in pathways such as FGF, PTN, WNT, PROS, PERIOSTIN, and TGFb. Endothelial cells and fibroblasts in -CBT are heterogeneous and involved in important cellular interactionprocesses, in which the discovery of FGF,PTN,WNT,PROS,PERIOSTIN and TGFb signals may play an important role in the regulation of microenvironment of -CBT.

摘要

为探究突变型颈动脉体瘤(-CBT)微环境中内皮细胞和成纤维细胞的基因表达特征,明确各亚群的功能富集情况,并进一步探索-CBT微环境中的细胞间相互作用网络。利用生物信息学分析方法下载并重新分析-CBT、突变型胸腹部副神经节瘤(-ATPGL)、-CBT和正常肾上腺髓质(NAM)的单核RNA测序数据,以阐明样本的细胞群体信息。我们重点探索内皮细胞和成纤维细胞亚群的基因表达谱,并基于基因本体论(GO)资源进行功能富集分析。使用CellChat比较不同临床样本的细胞间相互作用网络,并预测-CBT中显著的信号通路。共分析了7个细胞群体。-CBT中内皮细胞的主要亚型是动脉和静脉内皮细胞,成纤维细胞的主要亚型是肌成纤维细胞和周细胞。与NAM、-CBT和-ATPGL相比,-CBT中涉及内皮细胞和成纤维细胞的细胞通讯更为丰富,在FGF、PTN、WNT、PROS、骨膜蛋白和TGFb等通路中显著富集。-CBT中的内皮细胞和成纤维细胞具有异质性,参与重要的细胞相互作用过程,其中FGF、PTN、WNT、PROS、骨膜蛋白和TGFb信号的发现可能在-CBT微环境的调节中起重要作用。

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