Vascular endothelial cell development and diversity.
Vascular endothelial cell development and diversity.
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DOI：
10.1038/s41569-022-00770-1
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发表时间：
2023-03
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--
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血管内皮细胞形成血管内层，在功能循环系统的发育和维持中起着关键作用，并为周围的非血管细胞提供旁分泌支持。在过去的5年中，单细胞基因组学和体内基因标记的技术进步促进了对内皮细胞发育、可塑性和异质性的更深入的了解。这些进展也有助于重新理解内皮细胞亚型分化的时机及其与细胞周期的关系。内皮细胞中新的组织特异性基因表达模式的识别导致了关键信号通路的发现以及与其他类型细胞的新的相互作用，这些细胞类型在组织维持和疾病病理中都具有关键作用。在这篇综述中，我们描述了血管内皮细胞发育和多样性的最新发现，这些发现通常得到大规模的单细胞研究的支持，并讨论这些发现对血管医学的影响。此外，我们还重点介绍了单细胞多模式组学等技术是如何被用于研究正常血管生理学以及疾病中的功能紊乱的，这些技术在过去两年中变得越来越复杂。在过去的5年中，单细胞RNA测序技术的进步使人们对内皮细胞的发育和异质性有了更深入的了解。在这篇综述中，Red-Horse和Trimm讨论了关于血管内皮细胞发育和多样性的最新研究，并重点介绍了心脏、脑、肺、肾脏和肝脏中特定器官内皮细胞的最新发现。动脉分化与细胞周期停滞有关，新动脉在发育过程中通过从毛细血管和静脉招募内皮细胞来扩张。单细胞RNA测序(scRNA-seq)数据和多模式组学图谱提供了对组织内皮细胞异质性的洞察，以及发育过程中保守的转录代码。结合scRNA-seq的内皮细胞谱系追踪的新方法有助于识别肺、肝和肾脏中功能不同的毛细血管种群，以及它们对疾病的转录反应。毛细血管分区，即沿着一个轴的内皮细胞逐渐表型的连续体，已在包括脑、心脏和肝脏在内的多个器官中被发现，内皮细胞和壁细胞之间的通信在维持毛细血管分区和血脑屏障等重要结构方面起着关键作用。对人和小鼠的scRNA-seq图谱的比较表明，内皮细胞种群在多个器官的物种之间在很大程度上是保守的，尽管内皮细胞亚型存在独特的物种特异性基因表达模式，但物种之间的高度相似性表明了小鼠作为血管生物学模式生物的实用性。生物工程的进展导致了具有越来越多功能的血管系统的有机化合物的产生；来自单细胞研究的关键见解有望促进人类多能干细胞分化方案的改进，以及器官特异性血管系统的体外发展。
Vascular endothelial cells form the inner layer of blood vessels where they have a key role in the development and maintenance of the functional circulatory system and provide paracrine support to surrounding non-vascular cells. Technical advances in the past 5 years in single-cell genomics and in in vivo genetic labelling have facilitated greater insights into endothelial cell development, plasticity and heterogeneity. These advances have also contributed to a new understanding of the timing of endothelial cell subtype differentiation and its relationship to the cell cycle. Identification of novel tissue-specific gene expression patterns in endothelial cells has led to the discovery of crucial signalling pathways and new interactions with other cell types that have key roles in both tissue maintenance and disease pathology. In this Review, we describe the latest findings in vascular endothelial cell development and diversity, which are often supported by large-scale, single-cell studies, and discuss the implications of these findings for vascular medicine. In addition, we highlight how techniques such as single-cell multimodal omics, which have become increasingly sophisticated over the past 2 years, are being utilized to study normal vascular physiology as well as functional perturbations in disease. Advances in single-cell RNA sequencing technologies in the past 5 years have led to a greater understanding of endothelial cell development and heterogeneity. In this Review, Red-Horse and Trimm discuss the most up-to-date research on vascular endothelial cell development and diversity, and highlight the latest findings on organ-specific endothelial cells in the heart, brain, lungs, kidneys and liver. Artery differentiation is coupled to cell cycle arrest, and new arteries expand during development by recruiting endothelial cells from capillaries and veins. Single-cell RNA sequencing (scRNA-seq) data and multimodal omics atlases provide insights into the heterogeneity of endothelial cells across tissues, as well as conserved transcription codes during development. Novel methods of endothelial cell lineage tracing combined with scRNA-seq has facilitated the identification of functionally distinct capillary populations in the lung, liver and kidney, as well as their transcriptional response to disease. Capillary zonation, or the gradual phenotypic continuum of endothelial cells along an axis, has been identified in multiple organs including the brain, heart and liver, and communication between endothelial cells and mural cells has a key role in maintaining capillary zonation and important structures such as the blood–brain barrier. Comparison of scRNA-seq atlases from humans and mice reveals that endothelial cell populations are largely conserved between species across multiple organs and that although unique species-specific gene expression patterns exist for endothelial subtypes, the high degree of similarity between species demonstrates the utility of mice as a model organism for vascular biology. Advances in bioengineering have led to the creation of organoids with increasingly functional vasculature; key insights from single-cell studies are expected to facilitate improved differentiation protocols for human pluripotent stem cells as well as the in vitro development of organ-specific vasculature.
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影响因子：
4.6
作者：
Chen, Heidi I.;Sharma, Bikram;Red-Horse, Kristy
通讯作者：
Red-Horse, Kristy
影响因子：
64.5
作者：
Das, Soumyashree;Goldstone, Andrew B.;Red-Horse, Kristy
通讯作者：
Red-Horse, Kristy
影响因子：
5.4
作者：
Blanco, Raquel;Gerhardt, Holger
通讯作者：
Gerhardt, Holger
影响因子：
8.8
作者：
Cui, Yueli;Zheng, Yuxuan;Tang, Fuchou
通讯作者：
Tang, Fuchou
DOI：
10.1161/atvbaha.114.303218
发表时间：
2014-11-01
影响因子：
8.7
作者：
Corada, Monica;Morini, Marco Francesco;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta