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在胸腔和腹腔大动脉动脉瘤中,光滑肌肉表型调节的明显模式

Chien-Jung Lin^1,2, Campbell Keating², Robyn Roth³

¹Division of Cardiology, Department of Internal Medicine, SSM-Saint Louis University Hospital, St. Louis, MO 63110, USA.

Journal of cardiovascular development and disease

|November 26, 2024

概括

胸腔和腹腔大动脉动脉瘤具有不同的细胞特征. 一个独特的光滑肌肉细胞 (SMC) 群体,SMCmod,表达Igfbp2和Tnfrsf11b,在胸前动脉动脉瘤 (TAA) 中更为普遍,这表明TAA病变发生中的作用.

科学领域:

血管生物学血管生物学
基因组学就是基因组学.
蛋白质组学是指蛋白质组学.

背景情况:

胸前动脉动脉瘤 (TAA) 和腹部动脉动脉瘤 (AAA) 在形态上相似,但在临床和遗传方面有所不同.
大量RNA测序研究表明TAA和AAA组织中存在不同的基因表达模式,但缺乏细胞分辨率.
单细胞RNA测序 (scRNA-seq) 能够对细胞类型特定的转录组进行审讯,这对于理解诸如大动脉动脉瘤等复杂疾病至关重要.

研究的目的:

使用scRNA-seq. 调查胸腔动脉瘤和腹腔动脉瘤之间的细胞类型特定的转录组差异.
识别与TAA和AAA病变发生相关的独特细胞群和分子特征.
为了验证人类大动脉组织中的关键发现.

主要方法:

从小鼠TAA和AAA模型中获取和分析scRNA-seq数据集,以及来自基因表达大巴的控制.
使用Seurat 4,clusterProfiler和Connectome软件进行生物信息分析.
人类大动脉组织的免疫染,以验证关键识别标记物的蛋白质表达水平.

主要成果:

在正常和动脉瘤大动脉中识别了三个不同的光滑肌肉细胞 (SMC) 群体 (SMC1,SMC2,SMCmod).
与AAA (10-12%) 相比,TAA中观察到的SMCmod细胞比例 (38%) 显著更高.
SMCmod细胞表现出明显的转录特征,包括*Igfbp2*和*Tnfrsf11b*的上调表达,以及与细胞外矩阵组织和IGF运输相关的途径的丰富.

结论:

在它们的SMC种群中,TAA和AAA具有独特的细胞组成和转录基因特征.
*Igfbp2*和*Tnfrsf11b*基因与TAA SMCs有显著的关联,可能在TAA病原发生中发挥作用.
需要进一步的研究来阐明 *IGFBP2* 和 *TNFRSF11B* 在大动脉动脉瘤发育中的特定病原遗传作用.

关键词:

一个大动脉动脉瘤.一个单细胞RNA测序.顺肌细胞是平滑肌肉细胞.

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