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

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...

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Main Authors: Miriam Bracha Ginzberg, Nancy Chang, Heather D'Souza, Nish Patel, Ran Kafri, Marc W Kirschner
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/26957
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author Miriam Bracha Ginzberg
Nancy Chang
Heather D'Souza
Nish Patel
Ran Kafri
Marc W Kirschner
author_facet Miriam Bracha Ginzberg
Nancy Chang
Heather D'Souza
Nish Patel
Ran Kafri
Marc W Kirschner
author_sort Miriam Bracha Ginzberg
collection DOAJ
description 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.
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spelling doaj.art-5c836f7e150042c1a45da7a79e6e4da72022-12-22T02:02:48ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.26957Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformityMiriam Bracha Ginzberg0https://orcid.org/0000-0001-8431-3714Nancy Chang1Heather D'Souza2Nish Patel3Ran Kafri4https://orcid.org/0000-0002-9656-0189Marc W Kirschner5https://orcid.org/0000-0001-6540-6130Department of Systems Biology, Harvard Medical School, Boston, United States; Cell Biology Program, The Hospital for Sick Children, Toronto, CanadaCell Biology Program, The Hospital for Sick Children, Toronto, CanadaCell Biology Program, The Hospital for Sick Children, Toronto, CanadaCell Biology Program, The Hospital for Sick Children, Toronto, CanadaCell Biology Program, The Hospital for Sick Children, Toronto, CanadaDepartment of Systems Biology, Harvard Medical School, Boston, United StatesCell 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.https://elifesciences.org/articles/26957cell size controlcell growthcell cycle regulationgrowth rate regulationmammalian cells
spellingShingle Miriam Bracha Ginzberg
Nancy Chang
Heather D'Souza
Nish Patel
Ran Kafri
Marc W Kirschner
Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
eLife
cell size control
cell growth
cell cycle regulation
growth rate regulation
mammalian cells
title Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
title_full Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
title_fullStr Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
title_full_unstemmed Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
title_short Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
title_sort cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
topic cell size control
cell growth
cell cycle regulation
growth rate regulation
mammalian cells
url https://elifesciences.org/articles/26957
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