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通过单细胞 RNA 测序鉴定的小鼠静脉血栓形成的静脉壁细胞图谱。

A vein wall cell atlas of murine venous thrombosis determined by single-cell RNA sequencing.

机构信息

Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53705, USA.

Department of Surgery, Division of Vascular Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.

出版信息

Commun Biol. 2023 Jan 31;6(1):130. doi: 10.1038/s42003-023-04492-z.

DOI:10.1038/s42003-023-04492-z
PMID:36721040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9889765/
Abstract

Deep vein thrombosis (DVT) is a common clinical problem, but its cellular and molecular mechanisms remain incompletely understood. In this study, we performed single-cell RNA sequencing on mouse inferior vena cava (IVC) 24 h after thrombus-inducing IVC ligation or sham operation. 9 cell types composed of multiple subpopulations were identified. Notable transcriptomic changes induced by DVT included a marked inflammatory response, elevated hypoxia, and globally reduced myogenesis. Analysis of individual cell populations revealed increased inflammation and reduced extracellular matrix production across smooth muscle cells and fibroblasts, juxtaposed against an early phenotypic shift in smooth muscle cell populations away from a contractile state. By characterizing the transcriptomic changes in the vein wall during acute venous thrombosis at the single-cell level, this work provides novel insights into early pathological events in the vein wall that may potentiate thrombus formation and result in long term adverse venous remodeling.

摘要

深静脉血栓形成(DVT)是一种常见的临床问题,但其细胞和分子机制仍不完全清楚。在这项研究中,我们对血栓诱导的小鼠下腔静脉(IVC)结扎或假手术后 24 小时的 IVC 进行了单细胞 RNA 测序。鉴定出 9 种由多个亚群组成的细胞类型。DVT 引起的显著转录组变化包括明显的炎症反应、缺氧升高和整体肌生成减少。对单个细胞群的分析表明,平滑肌细胞和成纤维细胞的炎症增加,细胞外基质生成减少,而平滑肌细胞群的表型早期发生变化,从收缩状态转变。通过在单细胞水平上描述急性静脉血栓形成过程中静脉壁的转录组变化,本工作为静脉壁早期病理事件提供了新的见解,这些事件可能增强血栓形成并导致长期的静脉重塑不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/9b34bc7b8f4e/42003_2023_4492_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/65fd48e75c86/42003_2023_4492_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/b350aebe698f/42003_2023_4492_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/93bad13b8d4e/42003_2023_4492_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/f666b80b4e1b/42003_2023_4492_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/a6da0d3e5427/42003_2023_4492_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/9b34bc7b8f4e/42003_2023_4492_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/65fd48e75c86/42003_2023_4492_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/b350aebe698f/42003_2023_4492_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/93bad13b8d4e/42003_2023_4492_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/f666b80b4e1b/42003_2023_4492_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/a6da0d3e5427/42003_2023_4492_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c6/9889765/9b34bc7b8f4e/42003_2023_4492_Fig6_HTML.jpg

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