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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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Autores principales: Ginzberg, Miriam Bracha, Chang, Nancy, D'Souza, Heather, Patel, Nish, Kafri, Ran, Kirschner, Marc W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031432/
https://www.ncbi.nlm.nih.gov/pubmed/29889021
http://dx.doi.org/10.7554/eLife.26957
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author Ginzberg, Miriam Bracha
Chang, Nancy
D'Souza, Heather
Patel, Nish
Kafri, Ran
Kirschner, Marc W
author_facet Ginzberg, Miriam Bracha
Chang, Nancy
D'Souza, Heather
Patel, Nish
Kafri, Ran
Kirschner, Marc W
author_sort Ginzberg, Miriam Bracha
collection PubMed
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 pubmed-60314322018-07-06 Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity Ginzberg, Miriam Bracha Chang, Nancy D'Souza, Heather Patel, Nish Kafri, Ran Kirschner, Marc W eLife Cell Biology 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. eLife Sciences Publications, Ltd 2018-06-11 /pmc/articles/PMC6031432/ /pubmed/29889021 http://dx.doi.org/10.7554/eLife.26957 Text en © 2018, Ginzberg et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Ginzberg, Miriam Bracha
Chang, Nancy
D'Souza, Heather
Patel, Nish
Kafri, Ran
Kirschner, Marc W
Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
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 Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031432/
https://www.ncbi.nlm.nih.gov/pubmed/29889021
http://dx.doi.org/10.7554/eLife.26957
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