Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
Cell Mol Life Sci. 2022 Jun 20;79(7):372. doi: 10.1007/s00018-022-04403-1.
Dynamic brain activity requires timely communications between the brain parenchyma and circulating blood. Brain-blood communication is facilitated by intricate networks of brain vasculature, which display striking heterogeneity in structure and function. This vascular cell heterogeneity in the brain is fundamental to mediating diverse brain functions and has long been recognized. However, the molecular basis of this biological phenomenon has only recently begun to be elucidated. Over the past century, various animal species and in vitro systems have contributed to the accumulation of our fundamental and phylogenetic knowledge about brain vasculature, collectively advancing this research field. Historically, dye tracer and microscopic observations have provided valuable insights into the anatomical and functional properties of vasculature across the brain, and these techniques remain an important approach. Additionally, recent advances in molecular genetics and omics technologies have revealed significant molecular heterogeneity within brain endothelial and perivascular cell types. The combination of these conventional and modern approaches has enabled us to identify phenotypic differences between healthy and abnormal conditions at the single-cell level. Accordingly, our understanding of brain vascular cell states during physiological, pathological, and aging processes has rapidly expanded. In this review, we summarize major historical advances and current knowledge on blood endothelial cell heterogeneity in the brain, and discuss important unsolved questions in the field.
大脑的动态活动需要脑实质和循环血液之间进行及时的通讯。脑-血通讯是由错综复杂的脑脉管系统网络来促进的，其在结构和功能上具有显著的异质性。这种大脑中的血管细胞异质性对于调节多样化的大脑功能至关重要，并且长期以来一直受到关注。然而，这种生物学现象的分子基础直到最近才开始被阐明。在过去的一个世纪中，各种动物物种和体外系统为我们积累了关于脑脉管系统的基础和系统发育知识做出了贡献，共同推动了这一研究领域的发展。从历史上看，染料示踪剂和显微镜观察为了解大脑脉管系统的解剖和功能特性提供了有价值的见解，这些技术仍然是一种重要的方法。此外，分子遗传学和组学技术的最新进展揭示了脑内皮细胞和周细胞类型中的显著分子异质性。这些传统和现代方法的结合使我们能够在单细胞水平上识别健康和异常条件之间的表型差异。因此，我们对生理、病理和衰老过程中脑血管细胞状态的理解迅速扩展。在这篇综述中，我们总结了大脑中血液内皮细胞异质性的主要历史进展和当前知识，并讨论了该领域的重要未解决问题。
