核压缩介导的DNA损伤驱动ATR依赖的拉明表达和小鼠ESC差异化
Tanusri Roy1, Swetlana Ghosh1, Niyati Piplani1
1Department of Biosciences & Bioengineering, IIT Bombay, Mumbai 400076, India.
Nucleic acids research
|September 9, 2025
概括
硬的环境会通过核压缩对胚胎干细胞 (ESC) 造成DNA损伤,从而引发分化. 这一过程涉及ATR和CHK1DNA损伤反应 (DDR) 途径,影响拉敏A/C表达.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 发展生物学 发展生物学
背景情况:
- 胚胎干细胞 (ESC) 具有对生存至关重要的DNA损伤反应 (DDR).
- 物理力量对DNA损伤和ESC命运的影响尚不清楚.
研究的目的:
- 研究基质刚度如何影响小鼠ESC (mESC) 的DNA损伤和分化.
- 阐明ATR/CHK1 DDR路径在度介导的mESC差异化中的作用.
主要方法:
- 利用不同的基板刚度来诱导mESC中的差异扩散和核压缩.
- 评估了DNA损伤,DDR因子激活 (ATR,CHK1) 和拉胺A/C表达.
- 采用ATR和CHK1抑制剂来确定它们在分化中的作用.
主要成果:
- 基质刚性通过核压缩诱导mESC中的DNA损伤,导致分化.
- 与DNA损伤和ATR和CHK1.1激活相关的差异化.
- 抑制ATR或CHK1降低了lamine A/C表达,这表明途径参与.
结论:
- mESC分化是由核压缩诱导的DNA损伤驱动的.
- 这种依赖ATR的途径在硬度介导差异化过程中对调节拉米纳A/C起着关键作用.
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