UHRF1过度表达产生了不同的衰老状态,具有不同的TP53依赖性
Elena Magnani1, Charlene Chen1, Filippo Macchi1
1Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates.
bioRxiv : the preprint server for biology
|December 15, 2025
概括
来自UHRF1过度表达的表观遗传变化会产生多样化的衰老细胞. 这些细胞可以抑制或促进癌症,这取决于UHRF1水平和Tp53状态.
科学领域:
- 细胞衰老 细胞衰老
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 衰老是一种复杂的细胞状态,在抑制和促进癌症方面具有双重作用.
- 产生多样化的衰老细胞种群的机制仍然不清楚.
- UHRF1 (UHRF家族成员1) 是一种表观遗传调节器,涉及各种细胞过程.
研究的目的:
- 研究表观遗传失调,特别是UHRF1过度表达如何影响各种老化的细胞群的产生.
- 为了理解这些衰老细胞在新生前环境中的不同命运.
主要方法:
- 使用了一种具有肝细胞特异性UHRF1过度表达的先瘤斑马鱼肝脏模型.
- 分析了早期细胞反应,包括DNA损伤,DNA甲基化变化和细胞周期退出.
- 评估了衰老标志物,免疫特征,抗亡标志物和增殖基因表达.
- 研究了TP53 (瘤蛋白p53) 和UHRF1水平在决定细胞命运中的作用.
- 评估了老化药物Navitoclax的疗效.
主要成果:
- UHRF1的过度表达导致了双链断裂,DNA甲基化重塑模式,逆转移素激活,以及Atm/Tp53依赖的衰老.
- 不同的衰老细胞群体出现了:有些具有免疫/衰老特征和抗亡标记,另一些共同表达增殖基因.
- 由于Tp53的损失,衰老细胞的繁殖可能具有低的UHRF1,但不是高的UHRF1.
- 衰老的Navitoclax选择性地只针对衰老细胞的一个子集.
结论:
- 由UHRF1过度表达驱动的表观遗传变化会产生具有独特特征的异质衰老细胞群.
- 这些多样化的衰老细胞表现出不同的命运,影响瘤抑制或促进.
- 细胞衰老异质性受到表观遗传因素和Tp53状态的影响,影响治疗策略.
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