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Local cellular neighborhood controls proliferation in cell competition
Cell competition is a quality-control mechanism through which tissues eliminate unfit cells. Cell competition can result from short-range biochemical inductions or long-range mechanical cues. However, little is known about how cell-scale interactions give rise to population shifts in tissues, due to...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687024/ https://www.ncbi.nlm.nih.gov/pubmed/28931601 http://dx.doi.org/10.1091/mbc.E17-06-0368 |
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author | Bove, Anna Gradeci, Daniel Fujita, Yasuyuki Banerjee, Shiladitya Charras, Guillaume Lowe, Alan R. |
author_facet | Bove, Anna Gradeci, Daniel Fujita, Yasuyuki Banerjee, Shiladitya Charras, Guillaume Lowe, Alan R. |
author_sort | Bove, Anna |
collection | PubMed |
description | Cell competition is a quality-control mechanism through which tissues eliminate unfit cells. Cell competition can result from short-range biochemical inductions or long-range mechanical cues. However, little is known about how cell-scale interactions give rise to population shifts in tissues, due to the lack of experimental and computational tools to efficiently characterize interactions at the single-cell level. Here, we address these challenges by combining long-term automated microscopy with deep-learning image analysis to decipher how single-cell behavior determines tissue makeup during competition. Using our high-throughput analysis pipeline, we show that competitive interactions between MDCK wild-type cells and cells depleted of the polarity protein scribble are governed by differential sensitivity to local density and the cell type of each cell’s neighbors. We find that local density has a dramatic effect on the rate of division and apoptosis under competitive conditions. Strikingly, our analysis reveals that proliferation of the winner cells is up-regulated in neighborhoods mostly populated by loser cells. These data suggest that tissue-scale population shifts are strongly affected by cellular-scale tissue organization. We present a quantitative mathematical model that demonstrates the effect of neighbor cell–type dependence of apoptosis and division in determining the fitness of competing cell lines. |
format | Online Article Text |
id | pubmed-5687024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-56870242018-01-22 Local cellular neighborhood controls proliferation in cell competition Bove, Anna Gradeci, Daniel Fujita, Yasuyuki Banerjee, Shiladitya Charras, Guillaume Lowe, Alan R. Mol Biol Cell Articles Cell competition is a quality-control mechanism through which tissues eliminate unfit cells. Cell competition can result from short-range biochemical inductions or long-range mechanical cues. However, little is known about how cell-scale interactions give rise to population shifts in tissues, due to the lack of experimental and computational tools to efficiently characterize interactions at the single-cell level. Here, we address these challenges by combining long-term automated microscopy with deep-learning image analysis to decipher how single-cell behavior determines tissue makeup during competition. Using our high-throughput analysis pipeline, we show that competitive interactions between MDCK wild-type cells and cells depleted of the polarity protein scribble are governed by differential sensitivity to local density and the cell type of each cell’s neighbors. We find that local density has a dramatic effect on the rate of division and apoptosis under competitive conditions. Strikingly, our analysis reveals that proliferation of the winner cells is up-regulated in neighborhoods mostly populated by loser cells. These data suggest that tissue-scale population shifts are strongly affected by cellular-scale tissue organization. We present a quantitative mathematical model that demonstrates the effect of neighbor cell–type dependence of apoptosis and division in determining the fitness of competing cell lines. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687024/ /pubmed/28931601 http://dx.doi.org/10.1091/mbc.E17-06-0368 Text en © 2017 Bove, Gradeci, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Bove, Anna Gradeci, Daniel Fujita, Yasuyuki Banerjee, Shiladitya Charras, Guillaume Lowe, Alan R. Local cellular neighborhood controls proliferation in cell competition |
title | Local cellular neighborhood controls proliferation in cell competition |
title_full | Local cellular neighborhood controls proliferation in cell competition |
title_fullStr | Local cellular neighborhood controls proliferation in cell competition |
title_full_unstemmed | Local cellular neighborhood controls proliferation in cell competition |
title_short | Local cellular neighborhood controls proliferation in cell competition |
title_sort | local cellular neighborhood controls proliferation in cell competition |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687024/ https://www.ncbi.nlm.nih.gov/pubmed/28931601 http://dx.doi.org/10.1091/mbc.E17-06-0368 |
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