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Modularity and predictability in cell signaling and decision making

Cells make decisions to differentiate, divide, or apoptose based on multiple signals of internal and external origin. These decisions are discrete outputs from dynamic networks comprised of signaling pathways. Yet the validity of this decomposition of regulatory proteins into distinct pathways is un...

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Detalles Bibliográficos
Autores principales: Atay, Oguzhan, Skotheim, Jan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230600/
https://www.ncbi.nlm.nih.gov/pubmed/25368418
http://dx.doi.org/10.1091/mbc.E14-02-0718
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author Atay, Oguzhan
Skotheim, Jan M.
author_facet Atay, Oguzhan
Skotheim, Jan M.
author_sort Atay, Oguzhan
collection PubMed
description Cells make decisions to differentiate, divide, or apoptose based on multiple signals of internal and external origin. These decisions are discrete outputs from dynamic networks comprised of signaling pathways. Yet the validity of this decomposition of regulatory proteins into distinct pathways is unclear because many regulatory proteins are pleiotropic and interact through cross-talk with components of other pathways. In addition to the deterministic complexity of interconnected networks, there is stochastic complexity arising from the fluctuations in concentrations of regulatory molecules. Even within a genetically identical population of cells grown in the same environment, cell-to-cell variations in mRNA and protein concentrations can be as high as 50% in yeast and even higher in mammalian cells. Thus, if everything is connected and stochastic, what hope could we have for a quantitative understanding of cellular decisions? Here we discuss the implications of recent advances in genomics, single-cell, and single-cell genomics technology for network modularity and cellular decisions. On the basis of these recent advances, we argue that most gene expression stochasticity and pathway interconnectivity is nonfunctional and that cellular decisions are likely much more predictable than previously expected.
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spelling pubmed-42306002015-01-20 Modularity and predictability in cell signaling and decision making Atay, Oguzhan Skotheim, Jan M. Mol Biol Cell Perspectives Cells make decisions to differentiate, divide, or apoptose based on multiple signals of internal and external origin. These decisions are discrete outputs from dynamic networks comprised of signaling pathways. Yet the validity of this decomposition of regulatory proteins into distinct pathways is unclear because many regulatory proteins are pleiotropic and interact through cross-talk with components of other pathways. In addition to the deterministic complexity of interconnected networks, there is stochastic complexity arising from the fluctuations in concentrations of regulatory molecules. Even within a genetically identical population of cells grown in the same environment, cell-to-cell variations in mRNA and protein concentrations can be as high as 50% in yeast and even higher in mammalian cells. Thus, if everything is connected and stochastic, what hope could we have for a quantitative understanding of cellular decisions? Here we discuss the implications of recent advances in genomics, single-cell, and single-cell genomics technology for network modularity and cellular decisions. On the basis of these recent advances, we argue that most gene expression stochasticity and pathway interconnectivity is nonfunctional and that cellular decisions are likely much more predictable than previously expected. The American Society for Cell Biology 2014-11-05 /pmc/articles/PMC4230600/ /pubmed/25368418 http://dx.doi.org/10.1091/mbc.E14-02-0718 Text en © 2014 Atay and Skotheim. 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 Perspectives
Atay, Oguzhan
Skotheim, Jan M.
Modularity and predictability in cell signaling and decision making
title Modularity and predictability in cell signaling and decision making
title_full Modularity and predictability in cell signaling and decision making
title_fullStr Modularity and predictability in cell signaling and decision making
title_full_unstemmed Modularity and predictability in cell signaling and decision making
title_short Modularity and predictability in cell signaling and decision making
title_sort modularity and predictability in cell signaling and decision making
topic Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230600/
https://www.ncbi.nlm.nih.gov/pubmed/25368418
http://dx.doi.org/10.1091/mbc.E14-02-0718
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