双血统追踪确定了与动脉硬化损伤组成的辐射相关变化背后的细胞机制
bioRxiv : the preprint server for biology
|February 6, 2026
概括
一个新的双谱追踪模型显示,辐射会导致光滑肌细胞失去损伤投资,内皮细胞扩大,导致动脉样硬化斑块不稳定. 这一发现澄清了细胞动态和与放射治疗相关的潜在风险.
科学领域:
- 血管生物学 血管生物学
- 动脉样硬化研究 动脉样硬化研究
- 细胞可塑性 细胞可塑性
背景情况:
- 光滑肌细胞 (SMC) 和内皮细胞 (EC) 的表型可塑性影响动脉样硬化斑块的稳定性.
- 了解这些细胞类型在压力 (例如,辐射) 下如何相互影响是有限的.
- 在同一区域内同时绘制SMC和EC的命运地图一直是一个重大挑战.
研究的目的:
- 开发和使用双谱追踪小鼠模型,同时绘制SMC和EC的命运.
- 在动脉样硬化背景下调查对辐射的协调SMC和EC反应.
- 为了确定细胞机制,有助于辐射后斑块不稳定.
主要方法:
- 产生双谱追踪的阿波缺乏的小鼠,同时进行SMC和EC命运映射.
- 通过辐射,骨髓移植和西方饮食诱导动脉样硬化.
- 应用谱系追踪,免疫染色和单细胞RNA测序 (scRNA-seq) 进行分析.
主要成果:
- 双谱追踪成功同时标记SMC和EC衍生细胞.
- 辐射导致SMC衍生细胞降低损伤投资的调节,并提高炎症基因的调节.
- 来自EC的细胞扩大并表达了SMC相关基因,但未能调高细胞外基因矩阵基因,从而降低了斑块原蛋白含量.
结论:
- 辐射诱导的SMC损失和EC扩张不是血统分配的工件.
- SMC炎症重编程和EC表型调制有助于细胞外矩阵组织受损.
- 这些发现可能解释了放射治疗后动脉样硬化心血管疾病风险的增加.
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