轻度缺血性卒中患者的循环免疫细胞景观

IF 2.6 1区 医学 Journal of Investigative Medicine Pub Date : 2022-03-09 DOI:10.1136/svn-2021-001224
Young-Eun Cho, Hyangkyu Lee, Heekyong R. Bae, Hyungsuk Kim, S. Yun, Rany Vorn, A. Cashion, M. J. Rucker, M. Afzal, L. Latour, J. Gill
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引用次数: 7

摘要

轻度缺血性脑卒中患者出现轻微或缓解症状,有时未得到诊断,被排除在治疗之外,在某些情况下临床恶化。循环免疫细胞是潜在的生物标志物,可以帮助诊断缺血性中风。了解由缺血性中风引起的每个细胞群的转录组变化是至关重要的,因为它们在一个复杂的关系中密切合作。在这项研究中,我们使用单细胞RNA测序研究了中风患者外周血单核细胞(PBMCs)转录组学,以无偏倚的方式了解轻度中风后基于基因表达的外周免疫反应。方法将10例急性缺血性脑卒中发病后24小时内的pbmcs转录组与9个种族匹配/年龄匹配/性别匹配的对照组进行比较。单个pbmc用ddSeqTM (Illumina- biorad)制备,并在Illumina NovaSeq 6000平台上测序。结果在脑卒中患者中观察到明显的群体变化,特别是NK细胞和CD14+单核细胞。NK细胞数量增加,流式细胞术进一步证实。功能分析表明,中风患者的NK细胞活性也有所增强。CD14+单核细胞聚集成两组;树突状细胞相关CD14+单核细胞和NK细胞相关CD14+单核细胞。我们发现CD14+单核细胞亚群在中风患者中显著减少。这是第一个基于转录组学分析证明轻度缺血性卒中中NK细胞和新的单核细胞亚群数量增加的研究。我们的研究结果提供了循环免疫反应的动力学,可以帮助轻度缺血性中风的诊断和潜在的治疗发展。
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Circulating immune cell landscape in patients who had mild ischaemic stroke
Introduction Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed, are excluded from treatment and in some cases clinically worsen. Circulating immune cells are potential biomarkers that can assist with diagnosis in ischaemic stroke. Understanding the transcriptomic changes of each cell population caused by ischaemic stroke is critical because they work closely in a complicated relationship. In this study, we investigated peripheral blood mononuclear cells (PBMCs) transcriptomics of patients who had a stroke using a single-cell RNA sequencing to understand peripheral immune response after mild stroke based on the gene expression in an unbiased way. Methods Transcriptomes of PBMCsfrom 10 patients who had an acute ischaemic stroke within 24 hours after stroke onset were compared with 9 race-matched/age-matched/gender-matched controls. Individual PBMCs were prepared with ddSeqTM (Illumina-BioRad) and sequenced on the Illumina NovaSeq 6000 platform. Results Notable population changes were observed in patients who had a stroke, especially in NK cells and CD14+ monocytes. The number of NK cells was increased, which was further confirmed by flow cytometry. Functional analysis implied that the activity of NK cells also is enhanced in patients who had a stroke. CD14+ monocytes were clustered into two groups; dendritic cell-related CD14+ monocytes and NK cell-related CD14+ monocytes. We found CD14+ monocyte subclusters were dramatically reduced in patients who had a stroke. Discussion This is the first study demonstrating the increased number of NK cells and new monocyte subclusters of mild ischaemic stroke based on the transcriptomic analysis. Our findings provide the dynamics of circulating immune response that could assist diagnosis and potential therapeutic development of mild ischaemic stroke.
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来源期刊
Journal of Investigative Medicine
Journal of Investigative Medicine MEDICINE, GENERAL & INTERNALMEDICINE, RESE-MEDICINE, RESEARCH & EXPERIMENTAL
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111
期刊介绍: Journal of Investigative Medicine (JIM) is the official publication of the American Federation for Medical Research. The journal is peer-reviewed and publishes high-quality original articles and reviews in the areas of basic, clinical, and translational medical research. JIM publishes on all topics and specialty areas that are critical to the conduct of the entire spectrum of biomedical research: from the translation of clinical observations at the bedside, to basic and animal research to clinical research and the implementation of innovative medical care.
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