1. Cell Biology
  2. Computational and Systems Biology
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Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity

  1. Miriam Bracha Ginzberg
  2. Nancy Chang
  3. Heather D'Souza
  4. Nish Patel
  5. Ran Kafri  Is a corresponding author
  6. Marc W Kirschner  Is a corresponding author
  1. Harvard Medical School, United States
  2. The Hospital for Sick Children, Canada
Research Article
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Cite as: eLife 2018;7:e26957 doi: 10.7554/eLife.26957

Abstract

Cell size uniformity in healthy tissues suggests that control mechanisms might coordinate cell growth and division. We derived a method to assay whether cellular growth rates depend on cell size, by monitoring how variance in size changes as cells grow. Our data revealed that, twice during the cell cycle, growth rates are selectively increased in small cells and reduced in large cells, ensuring cell size uniformity. This regulation was also observed directly by monitoring nuclear growth in live cells. We also detected cell-size-dependent adjustments of G1 length, which further reduce variability. Combining our assays with chemical/genetic perturbations confirmed that cells employ two strategies, adjusting both cell cycle length and growth rate, to maintain the appropriate size. Additionally, although Rb signaling is not required for these regulatory behaviors, perturbing Cdk4 activity still influences cell size, suggesting that the Cdk4 pathway may play a role in designating the cell's target size.

Article and author information

Author details

  1. Miriam Bracha Ginzberg

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nancy Chang

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Heather D'Souza

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Nish Patel

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Ran Kafri

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    For correspondence
    ran.kafri@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-9656-0189
  6. Marc W Kirschner

    Department of Systems Biology, Harvard Medical School, Boston, United States
    For correspondence
    marc@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-6540-6130

Funding

Canadian Institutes of Health Research (FRN-343437)

  • Ran Kafri

National Institutes of Health (R01GM026875)

  • Marc W Kirschner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bruce Edgar, Reviewing Editor, University of Utah, United States

Publication history

  1. Received: March 18, 2017
  2. Accepted: June 7, 2018
  3. Accepted Manuscript published: June 11, 2018 (version 1)

Copyright

© 2018, Ginzberg et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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