在病毒和化学暴露时剖析人体免疫细胞中的表观基因组动态,通过多式单细胞分析进行多式单细胞分析
bioRxiv : the preprint server for biology
|September 18, 2025
概括
病毒和化学物质等环境暴露会改变免疫细胞基因调节. 这项研究使用单核图谱绘制了这些变化,揭示了与感染和疾病严重程度相关的T细胞和单细胞的表观遗传变化.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 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:
- 免疫细胞基因调节受到病原体和化学物质暴露的深刻影响.
- 了解这些动态变化对于破译免疫反应和疾病发病过程至关重要.
研究的目的:
- 创建一个全面的单核染色体可访问性地图的人类免疫细胞暴露于HIV-1,COVID-19,流感病毒和有机酸盐后.
- 研究由细胞外部刺激驱动的基因调控景观重塑.
- 整合表观遗传学数据 (染色体可访问性和DNA甲基化) 以实现免疫细胞反应的多模式视图.
主要方法:
- 从271,299个人类免疫细胞生成一个单核色素可访问性地图.
- 对319,420个候选监管要素及其动态可访问性的分析.
- 从匹配样本中整合单细胞DNA甲基化概况.
- 对HIV队列和SARS-CoV-2暴露个体的纵向分析.
主要成果:
- 确定了与免疫细胞状态的基因表达相关的动态色素可访问性变化.
- 揭示了HIV-1暴露个体T细胞耗尽的表观遗传特征,涉及FOXP转录因子.
- 在SARS-CoV-2暴露时观察到单细胞调节元素的转变,改变细胞因子网络调节 (NF-κB到AP-1).
- 创建了一个多式表观基因组图谱,展示T细胞和单细胞中的互补表观基因特征.
- 将DNA甲基化特征与染色体可访问性变化联系起来,突出显示严重COVID-19中AP1动机动态.
结论:
- 环境暴露会在人类免疫细胞中诱导显著的细胞特异性表观遗传重塑.
- 开发的地图集为感染和疾病期间的基因调节提供了关键的见解.
- 表观遗传特征,特别是涉及转录因子网络,是免疫细胞状态和疾病严重程度的关键指标,提供潜在的治疗点.
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