Single‐cell transcriptome analysis reveals tumoral microenvironment heterogenicity and hypervascularization in human carotid body tumor

生物 转录组 祖细胞 转分化 细胞生物学 人口 癌症研究 周细胞 激光捕获显微切割 表型 细胞 电池类型 病理 内皮干细胞 干细胞 基因表达 医学 基因 遗传学 环境卫生 体外
作者
Gaopo Cai,Zhaohui Hua,Linfeng Zhang,Yutian Chen,Xu Li,Ke Ma,Zongping Xia,Zhen Li
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:239 (4) 被引量:1
标识
DOI:10.1002/jcp.31175
摘要

Abstract Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single‐cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single‐cell RNA sequencing (scRNA‐seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia‐inducible factor‐1 (HIF‐1) and as well as an early EPCs cell‐like population expressing CD14 and vascular endothelial growth factor. In addition to HIF‐1‐related transcriptional protein expression, macrophages1 also display a neovasculogenesis‐promoting phenotype. SMCs included three populations showing platelet‐derived growth factor receptor beta and vimentin expression, indicative of a cancer‐associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA‐seq profiles, providing novel insights into the mechanisms underlying its formation.
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