Toward a granular molecular-anatomic map of the blood vasculature - single-cell RNA sequencing makes the leap.

Toward a granular molecular-anatomic map of the blood vasculature - single-cell RNA sequencing makes the leap.
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DOI:
10.48101/ujms.v127.9051
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发表时间:
2022
影响因子:
3.4
通讯作者:
Betsholtz C
Betsholtz C
中科院分区:
医学4区
文献类型:
--
作者:
Betsholtz C

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单细胞RNA测序(scRNAseq)标志着生理学和医学新时代的诞生。在可预见的未来,我们将确切地知道在组成我们身体的所有不同细胞类型和亚型中表达了什么样的基因,以及表达水平。我们还将了解特定的细胞状态,无论是发生在发育,组织修复还是疾病期间,都反映了基因表达的精确变化。在深刻影响生命科学的所有领域的同时,scRNAseq可能会导致血管生物学研究的特别飞跃。血管在所有器官中普遍存在并完成基本功能,但功能不同。需要内脏器官特异性血管适应和专业化。这些反过来又由血管的两个主要细胞构建块(内皮细胞和壁细胞)的差异基因表达决定。器官型脉管系统对于脑、肺、肾和肝中的思维、气体交换、尿液排泄和异生物质解毒等多种功能是必不可少的。除了器官型之外,血管细胞还沿血管动静脉轴沿着不同,称为带状化,这种差异对于血压和流量的调节是必不可少的。此外,基于基因表达的分子变化决定了血管生成、血管通透性和免疫细胞运输所必需的细胞活性状态,即发育、炎症和修复所必需的功能。这些不同水平的细胞异质性在血管细胞中产生了几乎无限的表型多样性。在这篇综述中,我总结并分析了scRNAseq在短短几年内为这一领域带来的影响,并指出它将把我们带到哪里。
Single-cell RNA sequencing (scRNAseq) marks the birth of a new era in physiology and medicine. Within foreseeable future, we will know exactly what genes are expressed – and at what levels – in all the different cell types and subtypes that make up our bodies. We will also learn how a particular cell state, whether it occurs during development, tissue repair, or disease, reflects precise changes in gene expression. While profoundly impacting all areas of life science, scRNAseq may lead to a particular leap in vascular biology research. Blood vessels pervade and fulfill essential functions in all organs, but the functions differ. Innumerable organ-specific vascular adaptations and specializations are required. These, in turn, are dictated by differential gene expression by the two principal cellular building blocks of blood vessels: endothelial cells and mural cells. An organotypic vasculature is essential for functions as diverse as thinking, gas exchange, urine excretion, and xenobiotic detoxification in the brain, lung, kidney, and liver, respectively. In addition to the organotypicity, vascular cells also differ along the vascular arterio-venous axis, referred to as zonation, differences that are essential for the regulation of blood pressure and flow. Moreover, gene expression-based molecular changes dictate states of cellular activity, necessary for angiogenesis, vascular permeability, and immune cell trafficking, i.e. functions necessary for development, inflammation, and repair. These different levels of cellular heterogeneity create a nearly infinite phenotypic diversity among vascular cells. In this review, I summarize and exemplify what scRNAseq has brought to the picture in just a few years and point out where it will take us.
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