Single-cell transcriptome of the basal murine carotid artery

Acute vascular injury is an unwelcome consequence of invasive treatments designed to alleviate symptoms of vascular stenosis. Resulting fibrotic scarring and neointima formation may result in loss of lumen diameter and diminished vascular function. Understanding of the key phases of acute inflammation, resolution and remodeling has the potential to minimise unwanted effects on the vasculature and therefore improve patient outcomes. The cellular landscape of blood vessels is highly hetergeneous in nature, and therefore data at single-cell resolution is of high relevance to this problem. Herein, the cellularity of murine carotid artery tissue is described in a cell- and time-resolved manner. Single-cell RNA-sequencing of carotid tissue isolated at time-points ranging from uninjured vessel to 14 days post-injury enabled the recapitulation of all stages of vascular injury. In these data, a sub-population of smooth muscle cells which also arises in atherosclerosis and myocardial infarction was identified. So-called stem cells/endothelial cells/monocytes (SEM) cells are candidates for repopulating injured vessels, and were amongst the most proliferative cell clusters following wire-injury of the carotid artery. Transcriptional signatures reflecting SEM gene expression patterns could also be detected in bulk RNA-sequencing of neointimal tissue isolated by laser capture microdissection. These data indicate that phenotypic plasticity of smooth muscle cells is highly important to the progression of lumen loss following acute vascular insult. Uninjured, homeostatic murine carotid arteries were isolated and subjected to single-cell RNA-sequencing.急性血管损伤是为缓解血管狭窄症状而实施的侵入性治疗所带来的不良并发症。由此引发的纤维化瘢痕与新生内膜形成，可导致管腔直径缩小、血管功能受损。明晰急性炎症、炎症消退与血管重塑的关键阶段，有望减轻血管受到的不良影响，进而改善患者预后。 血管的细胞组成本质上具有高度异质性，因此单细胞分辨率的数据集与该研究问题高度相关。 本数据集以细胞分辨率与时间分辨率相结合的方式，刻画了小鼠颈动脉组织的细胞构成。研究人员对从未损伤血管到损伤后14天多个时间点分离的颈动脉组织进行了单细胞RNA测序（single-cell RNA-sequencing），成功重现了血管损伤的全部进程。 在本数据集的数据中，研究人员鉴定出了一个平滑肌细胞亚群——该亚群同样会在动脉粥样硬化（atherosclerosis）与心肌梗死（myocardial infarction）中出现。所谓的干细胞/内皮细胞/单核细胞（stem cells/endothelial cells/monocytes, SEM）亚群，是损伤血管再填充的潜在细胞来源，且在颈动脉钢丝损伤后属于增殖活性最高的细胞簇之一。 通过激光捕获显微切割（laser capture microdissection）分离的新生内膜组织的批量RNA测序（bulk RNA-sequencing）数据中，同样可检测到反映SEM基因表达特征的转录特征。 本数据集的数据表明，平滑肌细胞的表型可塑性在急性血管损伤后管腔狭窄的进展过程中发挥着极为关键的作用。 研究人员同时分离了未受损伤的稳态小鼠颈动脉，并对其进行了单细胞RNA测序。