Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing.

Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing.
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血管形成和稳态中血管内皮细胞的细胞异质性和干细胞:单细胞RNA测序的见解。

DOI:
10.3389/fcell.2023.1146399
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发表时间:
2023
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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血管内皮细胞(EC)构成血管的内表面,对于新血管的形成和器官的稳态是必不可少的。内皮细胞在血管生成和体内平衡过程中在不同器官和血管树中显示出显着的表型异质性。单细胞RNA测序(scRNA-seq)技术的最新进展使人们对小鼠和人类的EC异质性有了新的认识。特别是,scRNA-seq已经确定了不同器官中动脉,静脉和毛细血管EC的新分子特征,以及以前未被识别的特殊EC亚型,如位于肺肺泡毛细血管中的气细胞。scRNA-seq还揭示了专门的组织驻留EC亚型的基因表达谱,这些亚型能够克隆扩增并有助于成人血管生成,这是一种从预先存在的脉管系统形成新血管的过程。已经在各种不同的小鼠组织中鉴定了这些专门的组织驻留EC,包括主动脉内皮、肝脏、心脏、肺、皮肤、骨骼肌、视网膜、脉络膜和脑。转录因子和信号通路也已确定在专门的组织驻地EC控制血管生成。此外,scRNA-seq还记录了EC在诸如癌症、年龄相关性黄斑变性、阿尔茨海默病、动脉粥样硬化和心肌梗死等疾病中的反应。scRNA-seq揭示的这些新发现有可能为与血管相关的不同疾病提供新的治疗靶点。本文综述了近年来对血管内皮细胞异质性和内皮干细胞与小鼠和人类血管生成和稳态相关性的研究进展,并对scRNA-seq技术的应用前景进行了展望。
Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed the gene expression profiles of specialized tissue-resident EC subtypes that are capable of clonal expansion and contribute to adult angiogenesis, a process of new vessel formation from the pre-existing vasculature. These specialized tissue-resident ECs have been identified in various different mouse tissues, including aortic endothelium, liver, heart, lung, skin, skeletal muscle, retina, choroid, and brain. Transcription factors and signaling pathways have also been identified in the specialized tissue-resident ECs that control angiogenesis. Furthermore, scRNA-seq has also documented responses of ECs in diseases such as cancer, age-related macular degeneration, Alzheimer’s disease, atherosclerosis, and myocardial infarction. These new findings revealed by scRNA-seq have the potential to provide new therapeutic targets for different diseases associated with blood vessels. In this article, we summarize recent advances in the understanding of the vascular endothelial cell heterogeneity and endothelial stem cells associated with angiogenesis and homeostasis in mice and humans, and we discuss future prospects for the application of scRNA-seq technology.
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