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人类动脉动脉样硬化的高维单细胞多模式景观

Alexander C Bashore¹, Hanying Yan², Chenyi Xue¹

¹Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).

Arteriosclerosis, thrombosis, and vascular biology

|February 22, 2024

概括

这项研究绘制了动脉样硬化斑块内的多种细胞类型,识别了不同的炎症和泡细胞子集. 研究结果揭示了症状和无症状患者之间的细胞差异,为动脉样硬化提供了新的治疗点.

科学领域:

心血管生物学心血管生物学
免疫学免疫学免疫学
细胞和分子医学是细胞和分子医学.

背景情况:

动脉样斑块是复杂的组织,具有异质的细胞混合.
对动脉样硬化病变中的细胞转录和表型景观的全面理解是有限的.

研究的目的:

为了全面描述人类动脉动脉样硬化的细胞格局.
了解多模式细胞身份及其与临床病理生理学的关联.

主要方法:

通过测序 (CITE-seq) 和单细胞RNA测序 (scRNA-seq) 进行转录体和表观体的结合细胞索引.
将所有细胞类型归类为人类大脑动脉样硬化病变 (n=21;13有症状).
开发了一种使用CD29,CD142和CD90的流细胞计画面板,以分离SMC衍生细胞.

主要成果:

确定了25种具有独特多原子特征的细胞群,包括巨细胞,T细胞,NK细胞,B细胞,内皮细胞,纤维细胞和光滑肌细胞 (SMC).
具有特征的巨细胞子集 (促炎,TREM2阳性泡细胞) 和SMC子集 (包括SMC衍生泡细胞).
在有症状和无症状患者中观察到炎症性SMC和减少的细胞巨细胞,经典激活的内皮细胞和收缩/调节的SMC衍生的细胞的丰富.

结论:

创建了动脉样硬化的细胞种群的多式地图,提供了关于细胞多样性,表型,位置,隔离和临床相关性的见解.
这些发现有助于将心血管疾病易感位点映射到特定细胞类型中.
确定了用于动脉样硬化治疗的新型分子和细胞治疗点.

关键词:

动脉样硬化动脉样硬化纤维细胞的细胞.巨细胞是一个巨细胞.一个单细胞分析.顺肌细胞是平滑肌肉细胞.

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