高细胞吞吐量,可编程固定揭示了RNA和蛋白质的共同调节与空间解析的NFκB伪信号
Nicholas Zhang, Mingshuang Wang, Dhruv Nambiar
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30322, USA.
APL bioengineering
|November 28, 2024
概括
研究人员发现NFκB信号传递中RNA和蛋白质水平之间的异步假定时间调节 (APR). 这种新的RNA-蛋白调节框架揭示了翻译时间如何适应细胞信号事件.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 系统生物学 系统生物学
背景情况:
- RNA和蛋白质水平在整个生物环境中显示了可变的相关性.
- 了解RNA-蛋白质动态对于破译细胞功能至关重要.
研究的目的:
- 在细胞信号传递过程中研究RNA和蛋白质水平之间的时间关系.
- 为了确定控制RNA转化对刺激的反应的新型调节机制.
主要方法:
- 开发了一种时间序列固定方法,将静态刺激和可编程甲 perfusion 结合起来,用于单细胞分析 (pSigOmics).
- 利用单分子空间成像观察小鼠纤维细胞中的NFκB信号通路.
- 实现图形神经网络模型和决策树分类器用于数据分析.
主要成果:
- 发现了NFκB p65蛋白的RNA和蛋白质水平之间的异步伪性调节 (APR).
- 确认了正规NFκB通路动态和确定了A20抑制剂活性.
- 在静态和动态实验设置中展示了APR,使持续响应测量成为可能.
- 使用基于GAPDHRNA表达的图形神经网络成功预测APR细胞亚群.
结论:
- 建立了一个新的RNA-蛋白质监管框架,其中翻译时间适应信号事件.
- 阐明了在不同的细胞亚群中免疫信号的时间动态.
- 为RNA和蛋白质水平的基因表达调节的复杂性提供了新的见解.
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