MitoScribe单细胞分子记录器记录了线粒体DNA中的分级信号动态
Linhan Wang1, Nikolaos Poulis1, Deepak Srivastava1,2,3,4
1Gladstone Institutes, San Francisco, CA, USA.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
研究人员开发了MitoScribe,这是一种新的线粒体DNA (mtDNA) 记录系统. 这个平台精确地记录细胞信号,使得能够在单个细胞内详细重建过去的生物事件.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 基因编码的DNA记录器以基因组突变的形式捕捉短暂的生物事件.
- 现有的基于DNA的记录器在单个细胞内量化信号大小的能力有限.
研究的目的:
- 介绍MitoScribe,一个基于线粒体DNA (mtDNA) 的平台,用于高容量记录生物信号.
- 为了能够对单个细胞内的分子信号进行敏感,非破坏性和持久的测量.
主要方法:
- 利用线粒体DNA (mtDNA) 基编辑器 (DdCBEs) 将中性单核酸替代物引入mtDNA.
- 利用每细胞mtDNA的高拷贝数来进行信号放大和记录.
- 集成的MitoScribe与单细胞RNA测序和线粒体转录丰富.
主要成果:
- MitoScribe展示了分子信号的可重复性,灵敏性和高通量记录,如缺氧和各种信号通路.
- 启用了独立信号的多重记录和重叠信号的巧合检测.
- 重建了单细胞信号动态,并将早期分化的异质性与人类iPSC分化的晚期细胞状态联系起来.
结论:
- MitoScribe提供了一个可扩展的平台,用于复杂的细胞环境中的高分辨率分子记录.
- 为研究细胞信号动态和异质性提供了强大的工具.
- 促进对细胞命运决策和生物过程的更深入的理解.
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