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Cell size sensing in animal cells coordinates anabolic growth rates with cell cycle progression to maintain uniformity of cell size

Miriam B. Ginzberg, Nancy Chang, View ORCID ProfileRan Kafri, View ORCID ProfileMarc W. Kirschner
doi: https://doi.org/10.1101/123851
Miriam B. Ginzberg
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
2Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
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Nancy Chang
2Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
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Ran Kafri
2Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
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  • For correspondence: ran.kafri@sickkids.ca marc@hms.harvard.edu
Marc W. Kirschner
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
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  • ORCID record for Marc W. Kirschner
  • For correspondence: ran.kafri@sickkids.ca marc@hms.harvard.edu
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Abstract

The uniformity of cell size in healthy tissues suggests that control mechanisms might coordinate cell growth and division. We derived a method to assay whether growth rates of individual cells depend on cell size, by combining time-lapse microscopy and immunofluorescence to monitor how variance in cell size changes as cells grow. This analysis revealed two periods in the cell cycle when cell size variance decreases in a manner incompatible with unregulated growth, suggesting that cells sense their own size and adjust their growth rate to correct aberrations. Monitoring nuclear growth in live cells confirmed that these decreases in variance reflect a process that selectively inhibits the growth of large cells while accelerating growth of small cells. We also detected cell-size-dependent adjustments of G1 length, which further reduce variability. Combining our assays with chemical and genetic perturbations confirmed that cells employ two strategies, adjusting both cell cycle length and growth rate, to maintain the appropriate size.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 03, 2017.
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Cell size sensing in animal cells coordinates anabolic growth rates with cell cycle progression to maintain uniformity of cell size
Miriam B. Ginzberg, Nancy Chang, Ran Kafri, Marc W. Kirschner
bioRxiv 123851; doi: https://doi.org/10.1101/123851
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Cell size sensing in animal cells coordinates anabolic growth rates with cell cycle progression to maintain uniformity of cell size
Miriam B. Ginzberg, Nancy Chang, Ran Kafri, Marc W. Kirschner
bioRxiv 123851; doi: https://doi.org/10.1101/123851

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