单个血管细胞的表观基因格局反映了发育起源,并确定了疾病风险位置
bioRxiv : the preprint server for biology
|July 14, 2025
概括
血管细胞根据其位置表现出独特的表观遗传和基因表达模式,影响疾病易感性. 这项研究揭示了影响血管疾病遗传风险的特定区域的监管因素.
科学领域:
- 基因组学和表观基因组学
- 血管生物学 血管生物学
- 心血管疾病研究研究
背景情况:
- 血管部位对诸如动脉样硬化和动脉瘤等疾病的易感性各异.
- 这些特定地点的疾病风险的生物基础尚不清楚.
- 发育起源可能会影响血管组织中的染色质可访问性和基因调节.
研究的目的:
- 为了研究细胞类型和血管部位特定的染色质可访问性和基因表达.
- 识别调控元素和转录因子网络,驱动特定地点的血管疾病风险.
- 探索血管部位对遗传变异对染色质可访问性的影响.
主要方法:
- 单细胞染色体可访问性 (scATAC-seq) 和基因表达 (scRNA-seq) 分析来自三个不同的部位的小鼠血管组织.
- 对差异色素可访问性,基因表达和基因调控网络 (GRNs) 的分析.
- 整合全基因组关联研究 (GWAS) 数据和深度学习模型 (ChromBPNet) 来预测变异效应.
主要成果:
- 在血管光滑肌细胞 (SMC),纤维细胞和内皮细胞中发现了细胞类型和血管部位特定的调节增强剂.
- 确定了胚胎起源的表观遗传标记和发育转录因子的差异性可访问性 (例如,Tbx20,Hand2,Gata4,Hoxb).
- 上升性大动脉纤维细胞显示出与SMAD2/3和TGFβ信号传递相关的独特表观遗传模式;血管部位修饰细胞类型转录对遗传变异的影响.
结论:
- 血管细胞的表观基因和转录基因格局是细胞类型和血管部位特异性的.
- 特定部位增强剂在控制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.
- 了解这些特定站点的调节机制是解读不同血管疾病易感性的关键.
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