巨细胞表型的表观遗传编程由STING-IRF3驱动炎症在上升的胸前大动脉剖析
bioRxiv : the preprint server for biology
|February 6, 2026
概括
巨细胞 (MΦs) 的表观遗传重编程通过促进炎症驱动上升胸前大动脉剖析 (ATAD). 针对MΦs中的STING-IRF3信号可能为ATAD预防提供一种新的治疗方法.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 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:
- 上升胸前大动脉解剖 (ATAD) 涉及显著的巨细胞 (MΦ) 积累和炎症.
- 在ATAD中维持促炎性MΦ激活的机制尚未完全理解.
- 天生的免疫细胞中的表观遗传记忆可能会导致持续的炎症状态.
研究的目的:
- 调查表观遗传重编程是否决定了ATAD中的MΦ表型命运.
- 确定表观遗传重编程对ATAD病原体的贡献.
- 阐明STING-IRF3信号轴在MΦ表观遗传编程中的作用.
主要方法:
- 人类大动脉组织的单细胞RNA测序 (对照,动脉瘤,剖析).
- 集成的单细胞RNA测序,ATAC测序和空间转录组学在ATAD的小鼠模型中.
- 对MΦ特异性Sting和Irf3小鼠进行分析,以评估STING-IRF3信号传输.
主要成果:
- ATAD组织显示出亲炎性MΦ偏差与受损的细胞MΦ分化.
- 单细胞ATAC测序揭示了染色质重塑有利于促炎基因.
- STING-IRF3信号调节MΦ表观遗传编程,促进炎症和大动脉破坏.
结论:
- 对MΦs的STING-IRF3介导的表观遗传编程是ATAD发展的关键机制.
- 针对MΦ表观遗传编程为ATAD提供了一个潜在的治疗策略.
- 了解MΦ可塑性对于开发用于大动脉剖析的新疗法至关重要.
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