血管光滑肌细胞动脉样硬化轨迹以单细胞分辨率为特征,确定疾病风险的因果转录和表观基因机制
bioRxiv : the preprint server for biology
|June 12, 2025
概括
这项研究绘制了动脉样硬化期间血管光滑肌细胞 (SMC) 的变化图,揭示了冠状动脉疾病 (CAD) 风险的关键遗传驱动因素,并确定TCF21是细胞转换中的关键基因.
科学领域:
- 心血管生物学 心血管生物学
- 遗传学 遗传学 是一个
- 单细胞基因组学 单细胞基因组学
背景情况:
- 血管光滑肌细胞 (SMCs) 与遗传性冠状动脉疾病 (CAD) 风险有关.
- SMCs表现出复杂的细胞状态过渡,有助于疾病表型.
研究的目的:
- 在CAD因果关系中调查SMC状态轨迹的遗传基础.
- 在小鼠模型中创建动脉样硬化症的全面的转录和表观遗传地图.
主要方法:
- 密集的时间过程单细胞RNA测序和表观基因组分析.
- 使用瓦丁顿-最佳运输 (WOT) 的概率性细胞命运建模.
- 转录因子 (TF) 网络分析和in silico扰动.
主要成果:
- 确定了驱动SMC状态变化的关键TF,这些变化与EMT,血管发育和昼夜节律有关.
- 集成小鼠数据与人类CAD遗传学,以精确确定疾病介导的SMC表型.
- 证明了TCF21在SMC前体细胞转换和CAD风险基因调节中的作用.
结论:
- 在单细胞分辨率下表征动脉样硬化,揭示动态SMC轨迹.
- 确定了导致CAD风险的遗传和表观遗传机制.
- 强调TCF21在SMC发展中的关键作用及其对CAD的贡献.
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