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哺乳动物组织单细胞蛋白质丰度调节的原理

Andrew Leduc¹, Gergana Shipkovenska², Yanxin Xu²

¹Departments of Bioengineering, Biology, Chemistry and Chemical Biology, Single Cell Proteomics Center, and Barnett Institute, Northeastern University, Boston, MA 02115, USA.

bioRxiv : the preprint server for biology

|September 26, 2025

概括

这项研究量化了4200多个细胞中的蛋白质合成和清除,揭示了蛋白质组的细胞特异性调节. 关键发现表明翻译和清除取决于细胞生长率,影响蛋白质的丰富性和功能.

科学领域:

分子生物学分子生物学
基因组学就是基因组学.
细胞生物学细胞生物学

背景情况:

蛋白质合成和清除对于基因表达调节至关重要.
在复杂组织中体内调节作用在很大程度上仍未被探索.

研究的目的:

系统量化蛋白质合成和清除在原始组织中的单个细胞.
了解不同类型的细胞如何在体内调节它们的蛋白质组.
研究RNA丰度,翻译和蛋白质清除对蛋白质变异的贡献.

主要方法:

在4200多个单细胞中系统量化蛋白质合成和清除.
集成与单细胞转录组学.
多模式测量用于定量分析和功能解释.

主要成果:

确定了翻译和蛋白质清除对细胞生长率的线性依赖.
证明了蛋白质丰富性的细胞类型特定调节,其中一些蛋白质由RNA,翻译或清除一致调节,而其他蛋白质因细胞类型而异.
观察到与蛋白质清除相关的蛋白质丰度的特定细胞类型,与年龄相关的变化.
发现蛋白质-蛋白质相关性明显强于mRNA-mRNA相关性,由蛋白质清除介导.
发现了特定于细胞类型的功能集群,表明了代谢过程的差异协调.

结论:

建立了蛋白质调节的组织原则,强调了翻译和蛋白质清除的作用.
蛋白质清除调节显著影响蛋白质-蛋白质相关性和功能聚类.
开发了一个可扩展的框架,用于研究哺乳动物组织中的蛋白质调节.

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