单细胞转录组学和遗传关联的综合性分析可以识别与血管疾病相关的细胞状态
Mark E Pepin1, William E Schwartzman2, Shi Fang2
1The Broad Institute of Harvard and MIT, Cambridge, MA, USA; Divisions of Genetics and Cardiovascular Medicine, Brigham & Women's Hospital, Boston, MA, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Atherosclerosis
|March 22, 2025
概括
这项研究揭示了使用单核RNA测序的胸前大动脉动脉瘤中独特的血管光滑肌细胞 (VSMC) 和纤维细胞亚群. 这些发现强调了细胞状态转换是血管疾病病原体的关键.
科学领域:
- 心血管生物学 心血管生物学
- 基因组学就是基因组学.
- 细胞和分子医学是细胞和分子医学.
背景情况:
- 血管疾病涉及细胞表型变化,单细胞技术揭示了内皮细胞 (EC) 和血管光滑肌细胞 (VSMC) 的异质性.
- 假设VSMC在动脉样硬化中会在收缩和合成状态之间转移,但驱动早期血管功能障碍的特定亚群仍然不清楚.
研究的目的:
- 为了识别不同的血管细胞亚群和中间状态,有助于早期血管功能障碍.
- 研究细胞状态转换在诸如胸前动脉动脉瘤 (TAA) 等血管疾病的发病过程中的作用.
主要方法:
- 综合单核RNA测序 (snRNA-seq) 来自正常,动脉瘤和动脉样硬化的人类上升胸前大动脉.
- 利用计算工具将全基因组关联研究 (GWAS) 数据与单核大动脉表达特征集成.
- 应用RNA轨迹分析,推断细胞状态之间的基因表达连续.
主要成果:
- 确定了十个不同的转录组群,包括三个具有差异基因表达的VSMC亚群.
- 在动脉瘤样本中发现了特定纤维细胞和VSMC亚群的丰富.
- 在VSMC和纤维细胞状态之间推断了表型连续,VSMC和纤维细胞C显示了与冠状动脉疾病 (CAD),血压和偏头痛相关的GWAS位点的丰富.
结论:
- 单核转录组学有效捕获多种血管细胞类型,优先考虑那些参与疾病发病的细胞类型.
- 在TAA中证明了增殖性VSMC的丰富,支持表型切换作为病理机制.
- 综合分析通过GWAS数据表明纤维细胞和VSMC细胞状态转换在血管疾病病原体中.
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