单个血管细胞的表观基因格局反映了发育起源和疾病风险位置
Chad S Weldy1,2, Soumya Kundu3,4, João Monteiro5
1Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA. weldyc@stanford.edu.
Molecular systems biology
|September 10, 2025
概括
这项研究表明,血管中的特定基因调节元素是细胞类型和位置的独特特征,影响疾病风险. 了解这些特定于特定位置的增强剂是解开血管疾病复杂遗传驱动因素的关键.
科学领域:
- 基因组学就是基因组学.
- 血管生物学 血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 血管部位对动脉样硬化和动脉瘤等疾病具有不同的易感性.
- 驱动特定部位疾病风险的潜在表观基因组和转录基因组因素在很大程度上仍未被探索.
研究的目的:
- 为了研究小鼠血管组织的细胞类型和血管部位特定的表观基因组和转录基因组景观.
- 为了确定与血管部位特异性疾病风险相关的调节增强剂和转录因子.
主要方法:
- 单细胞染色体可访问性 (scATAC-seq) 和基因表达概况 (scRNA-seq) 在三个不同的位置的小鼠血管组织上进行.
- 对表观基因增强剂,基因调控网络和转录因子 (TF) 模式可访问性的分析.
- 整合全基因组关联数据和深度学习 (ChromBPNet) 来预测对染色质可访问性的变异效应.
主要成果:
- 发现关键的调节增强剂对细胞类型和血管部位都具有特异性.
- 确定了胚胎起源的表观遗传标记,包括Tbx20,Hand2,Gata4和Hoxb家族成员等发育TF.
- 转录因子动图的可访问性在光滑肌肉,纤维细胞和内皮细胞的血管部位上有显著的变化.
- 预测的变异效应突出显示了富含特定TF图案足迹的基因组区域 (例如,MEF2A,SMAD3,HAND2).
结论:
- 细胞类型和血管部位特异性增强剂在调节血管疾病风险的遗传驱动因素方面发挥着至关重要的作用.
- 这项研究为了解不同血管环境如何促进疾病易感性提供了基础.
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