在大动脉动脉瘤和剖析中表观遗传诱导光滑肌细胞表型变化
Abhijit Chakraborty1,2, Yanming Li1,2, Chen Zhang1,2
1Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery (A.C., Y.L., C.Z., K.R.R., Y.L., S.X., W.L., H.G.V., L.Z., J.S.C., S.A.L., Y.H.S.), Baylor College of Medicine, Houston, TX.
Circulation
|August 9, 2023
概括
大动脉动脉瘤和剖析中的光滑肌肉细胞经历了表观遗传变化,从收缩型转变为炎症型. 细胞质DNA触发了这种转变,突出了大动脉疾病进展的关键机制.
科学领域:
- 心血管生物学
- 表观遗传学
- 细胞生物学
背景情况:
- 在大动脉动脉瘤和剖析 (AAD) 中观察到光滑肌肉细胞 (SMC) 的表型切换.
- 在AAD中,特定的SMC表型和潜在机制尚不清楚.
研究的目的:
- 调查AAD中SMC表型变化的转录和表观基因动态.
- 确定大动脉疾病中SMC表型变化的关键驱动因素.
主要方法:
- 单细胞RNA测序和ATAC-seq用于动脉素II诱导AD的小鼠模型.
- 使用单细胞RNA测序分析了人类上升胸部AAD组织.
- 进行了血统追踪和染色体重塑分析.
主要成果:
- 大动脉应激诱导SMC从收缩型转变为增殖型,产生ECM和炎症型.
- 由染色体重塑驱动的SMC转化为纤维细胞和巨细胞.
- 干扰素调节因子3 (IRF3) 被确定为通过细胞质DNA- STING- TBK1信号传递的收缩性- 炎症性表型转变的关键驱动因素.
- 在小鼠中,抑制STING通路阻止了炎症性SMC过渡,并保留了SMC种群.
结论:
- 在AAD中,SMC的表型变化是由表观遗传机制动态诱导的.
- 在AAD中,DNA损伤和细胞泄漏将SMC从收缩型转变为炎症型.
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