Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb;590(7847):649-654.
doi: 10.1038/s41586-021-03232-9. Epub 2021 Feb 24.

Spatiotemporal dissection of the cell cycle with single-cell proteogenomics

Diana Mahdessian #  1 , Anthony J Cesnik #  1   2   3 , Christian Gnann  1   3 , Frida Danielsson  1 , Lovisa Stenström  1 , Muhammad Arif  1 , Cheng Zhang  1 , Trang Le  1 , Fredric Johansson  1 , Rutger Schutten  1 , Anna Bäckström  1 , Ulrika Axelsson  1 , Peter Thul  1 , Nathan H Cho  3 , Oana Carja  2   3   4 , Mathias Uhlén  1 , Adil Mardinoglu  1   5 , Charlotte Stadler  1 , Cecilia Lindskog  6 , Burcu Ayoglu  1 , Manuel D Leonetti  3 , Fredrik Pontén  6 , Devin P Sullivan  1 , Emma Lundberg  7   8   9
Affiliations

Spatiotemporal dissection of the cell cycle with single-cell proteogenomics

Diana Mahdessian et al. Nature. 2021 Feb.

Erratum in

  • Author Correction: Spatiotemporal dissection of the cell cycle with single-cell proteogenomics.
    Mahdessian D, Cesnik AJ, Gnann C, Danielsson F, Stenström L, Arif M, Zhang C, Le T, Johansson F, Schutten R, Bäckström A, Axelsson U, Thul P, Cho NH, Carja O, Uhlén M, Mardinoglu A, Stadler C, Lindskog C, Ayoglu B, Leonetti MD, Pontén F, Sullivan DP, Lundberg E. Mahdessian D, et al. Nature. 2022 Aug;608(7924):E32. doi: 10.1038/s41586-022-05180-4. Nature. 2022. PMID: 35931766 No abstract available.

Abstract

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Malumbres, M. & Barbacid, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer 9, 153–166 (2009). - PubMed - DOI
    1. Massagué, J. G1 cell-cycle control and cancer. Nature 432, 298–306 (2004). - PubMed - DOI
    1. Hartwell, L. H. & Kastan, M. B. Cell cycle control and cancer. Science 266, 1821–1828 (1994). - PubMed - DOI
    1. Barnum, K. J. & O’Connell, M. J. in Cell Cycle Control Vol. 1170 (eds Noguchi, E. & Gadaleta, M. C.), 29–40 (Springer, 2014).
    1. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81, 323–330 (1995). - PubMed - DOI

Publication types

LinkOut - more resources