首页|内皮细胞和成纤维细胞介导颈动脉体副神经节瘤微环境调控网络研究

内皮细胞和成纤维细胞介导颈动脉体副神经节瘤微环境调控网络研究

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目的:探讨SDHD突变的颈动脉体副神经节瘤(SDHD-CBT)微环境中内皮细胞和成纤维细胞的基因表达特征,精细各亚群的功能富集情况,进一步探索SDHD-CBT微环境中细胞间相互调控网络.方法:采用生物信息学分析手段,下载并重新分析SDHD-CBT、SDHB突变的胸腹部副神经节瘤(SDHB-ATPGL)、SDHB-CBT和正常肾上腺髓质(NAM)的单细胞核RNA测序数据,明确样本的细胞群信息,重点探索内皮细胞和成纤维细胞亚群的基因表达特征,使用GO富集分析对亚群进行功能富集,并运用CellChat比较不同临床样本的细胞间相互调控网络,预测SDHD-CBT中的显著通路.结果:共获得7个细胞群,SDHD-CBT内皮细胞主要亚群是动脉和静脉内皮细胞,成纤维细胞主要亚群是肌成纤维细胞和周细胞.相比于NAM,SDHB-CBT和SDHB-ATPGL,SDHD-CBT中内皮细胞和成纤维细胞参与的细胞通讯更加丰富,显著富集FGF、PTN、WNT、PROS、PERIOSTIN和TGFb等通路.结论:SDHD-CBT中内皮细胞和成纤维细胞具有异质性,参与重要细胞通讯过程,其中,FGF、PTN、WNT、PROS、PERIOSTIN和TGFb通路的发现可能在SDHD-CBT微环境调控研究中起重要作用.
Endothelial cells and fibroblasts mediate the microenvironmental regulatory network of carotid body paraganglioma
Objective:To explore the gene expression characteristics of endothelial cells and fibroblasts in the microenvironment of SDHD-mutated carotid body tumors(SDHD-CBT),to fine the functional enrichment of each subcluster,and to further explore the network of cell-cell interactions in the microenvironment of SDHD-CBT.Methods:The bioinformatics analysis was used to download and reanalyze the single-nuclear RNA sequen-cing data of SDHD-CBT,SDHB mutated thoracic and abdominal paraganglioma(SDHB-ATPGL),SDHB-CBT,and normal adrenal medulla(NAM),to clarify the information of cell populations of the samples.We fo-cused 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 SDHD-CBT.Re-sults:A total of 7 cell populations were profiled.The main subtypes of endothelial cells in SDHD-CBT are arterial and venous endothelial cells,and the main subtypes of fibroblasts are myofibroblasts and pericytes.Compared to NAM,SDHB-CBT and SDHB-ATPGL,cell communication involving endothelial cells and fibroblasts in SDHD-CBT is more abundant,with significant enrichment in pathways such as FGF,PTN,WNT,PROS,PERIOSTIN,and TGFb.Conclusion:Endothelial cells and fibroblasts in SDHD-CBT are heterogeneous and in-volved 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 SDHD-CBT.

carotid body tumorssingle-nuclei RNA sequencingendothelial cellsfibroblastscell-cell interactome

张博雅、王圣明、胡怡冰、骆春雨、李世媛、楼梓涵、王菁菁、陈正侬、殷善开

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上海交通大学医学院附属第六人民医院耳鼻咽喉头颈外科(上海,200233)

颈动脉体副神经节瘤 单细胞核RNA测序 内皮细胞 成纤维细胞 细胞间相互调控

国家自然科学基金委面上项目上海市科学技术委员会上海市科学技术委员会

8207104022YF143270022Y11902100

2024

临床耳鼻咽喉头颈外科杂志
华中科技大学同济医学院附属协和医院

临床耳鼻咽喉头颈外科杂志

CSTPCD北大核心
影响因子:0.831
ISSN:1001-1781
年,卷(期):2024.38(9)