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人类大动脉细胞数量和转录组异质性的侧面和疾病依赖性变化,通过单细胞RNA测序确定

Nicolas Villa-Roel¹, Christian Park¹, Aitor Andueza¹

¹Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Health Sciences Research Bldg E170, Atlanta, GA 30322, USA.

|January 8, 2025

概括

动脉疾病 (CAVD) 由于明显的细胞差异,影响纤维侧更多. 向纤维细胞中的这些独特的膜内皮细胞 (VEC) 可能为CAVD提供新的治疗策略.

科学领域:

心血管生物学心血管生物学
分子医学是分子医学.
基因组学就是基因组学.

背景情况:

动脉疾病 (CAVD) 在老年人中很常见,缺乏有效的药物治疗方法.
CAVD主要影响主动脉的纤维化侧面,原因尚不清楚.
假设:侧依赖的转录基因和细胞差异使纤维细胞易于患有CAVD.

研究的目的:

在人类大动脉膜中研究侧依赖的转录和细胞表型.
确定纤维层中CAVD发展背后的机制.
发现CAVD的潜在治疗点.

主要方法:

从纤维化和心室侧面的内皮丰富样本的单细胞RNA测序.
分析了来自五个跨疾病谱的捐赠者的人类大动脉的说明书.
利用一种新的方法进行侧面特定的样本采集.

主要成果:

确定了27个细胞群,包括膜内皮细胞 (VEC),膜间歇细胞 (VIC) 和免疫细胞.
发现了具有明显基因表达的侧向依赖VEC亚型.
观察到炎症性VICs,巨细胞和T细胞随着CAVD进展的增加.
在患病叶片的纤维体中发现AP-1转录因子和EGR1的上调.
确定了与CAVD相关的VEC集群,与炎症,EMT,亡和纤维化有关.

结论:

膜内皮细胞 (VECs) 呈现出显著的异质性,取决于组织方面和CAVD状态.
病变膜纤维体中的独特的VEC集群和通路表明了新的致病机制.
纤维状VEC中的不同调节的基因和通路代表了CAVD的潜在治疗点.

关键词:

与AP-1相关的转录因子大动脉硬化症 (大动脉硬化症)甲状腺狭窄症是什么甲状腺膜疾病甲状腺膜疾病内皮细胞到介质细胞的过渡.人类大动脉门这是一种炎症炎症炎症炎症.一个单细胞RNA测序.转录组学转录组学是指转录组学.门内皮细胞的内皮细胞.门间歇细胞的间歇细胞

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RNA-seq

RNA-seq

RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...