Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
| Autor: | Diana Mahdessian, Fredrik Pontén, Mathias Uhlén, Manuel D. Leonetti, Fredric Johansson, Anna Bäckström, Christian Gnann, Frida Danielsson, Emma Lundberg, Lovisa Stenström, Peter Thul, Adil Mardinoglu, Nathan H. Cho, Cheng Zhang, Rutger Shutten, Devin P. Sullivan, Charlotte Stadler, Oana Carja, Trang Le, Ulrika Axelsson, Cecilia Lindskog, Anthony J. Cesnik, Muhammad Arif, Burcu Ayoglu |
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| Rok vydání: | 2021 |
| Předmět: |
Time Factors
Proteome Cell division Cell Mitosis Cell Cycle Proteins Cell fate determination Biology Proteomics Transcriptome 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Human proteome project medicine Humans Cell Lineage Phosphorylation Interphase Cell Proliferation Proteogenomics 030304 developmental biology Oncogene Proteins 0303 health sciences Multidisciplinary Cell growth Cell Cycle Cell cycle Cell biology medicine.anatomical_structure Single-Cell Analysis Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Nature. 590:649-654 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer1-3. 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. |
| Databáze: | OpenAIRE |
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