单细胞RNA测序揭示了不同的老型和在化疗后的转录组水平上的静止-衰老连续体
Brianna Fernandez1, Victor Passanisi1, Humza M Ashraf1
1Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
bioRxiv : the preprint server for biology
|June 4, 2025
概括
化疗诱导癌细胞的可逆静止和不可逆转衰老. 这项研究使用细胞循环成像和单细胞RNA测序来区分这些状态,揭示了细胞循环退出的连续性.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 基因组学就是基因组学.
背景情况:
- 静止和衰老是癌症治疗中关键的细胞循环停止状态.
- 由于缺乏特定的生物标志物,很难区分这些状态.
- 这两种状态都发生在化疗后,衰老抑制瘤,静止使治疗逃避.
研究的目的:
- 用先进的成像和测序技术来区分静止和衰老.
- 将异质细胞周期表型与化疗后的转录组景观联系起来.
- 阐明导致细胞循环停止的独特途径.
主要方法:
- 将细胞周期动态的时间间隔成像与单细胞RNA测序结合起来.
- 使用埃托胺治疗来诱导细胞循环停止.
- 使用伪时轨迹分析来建模细胞状态过渡.
主要成果:
- 确定了多种不同的老化类型 (老型) 并将它们与两个不同的逮捕途径联系起来.
- 揭示了线粒体转化到G0过渡后的渐进性停止途径和通过线粒体滑动的直接途径.
- 在逐渐停止的轨迹上表现出衰老表型的早期和逐渐表现,甚至在静止细胞中.
结论:
- 化疗诱导静止和衰老在一个连续的细胞循环撤回在转录组水平.
- 衰老的表型可以在细胞周期退出过程中早期出现.
- 理解这些状态对于开发有效的癌症疗法至关重要.
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