瑞典皇家理工学院Emma Lundberg研究组利用单细胞蛋白质组学解析出细胞周期的时空调控。2021年2月24日出版的《自然》杂志发表了这项成果。

通过整合亚细胞分辨率下的蛋白质组学与单细胞转录组学以及在细胞周期中单个细胞的精确时间测量，研究人员提供了人类蛋白质组学异质性的全面性时空图谱。结果表明，大约五分之一的人类蛋白质组显示出细胞间的变异性，研究人员鉴定出数百种与有丝分裂和细胞周期关联未知的蛋白质，并提供证据表明这些蛋白质中有几种具有致癌作用。细胞周期进程仅解释了所有细胞间变异性的一半不到，并且大多数周期蛋白在翻译后而不是通过转录组调控。

这些蛋白被调节细胞命运的激酶不成比例地磷酸化，而在细胞之间变化的非周期蛋白更可能被调节代谢的激酶修饰。细胞周期的这种空间分辨的蛋白质组图谱已整合到人类蛋白质图谱中，并将作为加速人类细胞周期和细胞增殖分子研究的资源。 

研究人员介绍，细胞生长和分裂的细胞周期是生命的基本过程。其失调会产生毁灭性后果，包括癌症。细胞周期是由蛋白质在时间和空间上的精确调节驱动的，这会在单个增殖细胞之间产生差异。目前还没有这种细胞间蛋白质组学变异性的系统研究。

附：英文原文

Title: Spatiotemporal dissection of the cell cycle with single-cell proteogenomics

Author: Diana Mahdessian, Anthony J. Cesnik, Christian Gnann, Frida Danielsson, Lovisa Stenstrm, Muhammad Arif, Cheng Zhang, Trang Le, Fredric Johansson, Rutger Shutten, Anna Bckstrm, Ulrika Axelsson, Peter Thul, Nathan H. Cho, Oana Carja, Mathias Uhln, Adil Mardinoglu, Charlotte Stadler, Cecilia Lindskog, Burcu Ayoglu, Manuel D. Leonetti, Fredrik Pontn, Devin P. Sullivan, Emma Lundberg

Issue&Volume: 2021-02-24

Abstract: The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer1,2,3. The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here we present a comprehensive, spatiotemporal map of human proteomic heterogeneity by integrating proteomics at subcellular resolution with single-cell transcriptomics and precise temporal measurements of individual cells in the cell cycle. We show that around one-fifth of the human proteome displays cell-to-cell variability, identify hundreds of proteins with previously unknown associations with mitosis and the cell cycle, and provide evidence that several of these proteins have oncogenic functions. Our results show that cell cycle progression explains less than half of all cell-to-cell variability, and that most cycling proteins are regulated post-translationally, rather than by transcriptomic cycling. These proteins are disproportionately phosphorylated by kinases that regulate cell fate, whereas non-cycling proteins that vary between cells are more likely to be modified by kinases that regulate metabolism. This spatially resolved proteomic map of the cell cycle is integrated into the Human Protein Atlas and will serve as a resource for accelerating molecular studies of the human cell cycle and cell proliferation.

DOI: 10.1038/s41586-021-03232-9

Source: https://www.nature.com/articles/s41586-021-03232-9