To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.

Cell fate determination is usually described as the result of the stochastic dynamics of gene regulatory networks (GRNs) reaching one of multiple steady-states each of which corresponds to a specific decision. However, the fate of a cell is determined in finite time suggesting the importance of tran...

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Autores principales:	Richard I Joh, Joshua S Weitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d086a28279b24dd8bcb13a56e4da7da1
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spelling	oai:doaj.org-article:d086a28279b24dd8bcb13a56e4da7da12021-11-18T05:50:40ZTo lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.1553-734X1553-735810.1371/journal.pcbi.1002006https://doaj.org/article/d086a28279b24dd8bcb13a56e4da7da12011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423715/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Cell fate determination is usually described as the result of the stochastic dynamics of gene regulatory networks (GRNs) reaching one of multiple steady-states each of which corresponds to a specific decision. However, the fate of a cell is determined in finite time suggesting the importance of transient dynamics in cellular decision making. Here we consider cellular decision making as resulting from first passage processes of regulatory proteins and examine the effect of transient dynamics within the initial lysis-lysogeny switch of phage λ. Importantly, the fate of an infected cell depends, in part, on the number of coinfecting phages. Using a quantitative model of the phage λ GRN, we find that changes in the likelihood of lysis and lysogeny can be driven by changes in phage co-infection number regardless of whether or not there exists steady-state bistability within the GRN. Furthermore, two GRNs which yield qualitatively distinct steady state behaviors as a function of phage infection number can show similar transient responses, sufficient for alternative cell fate determination. We compare our model results to a recent experimental study of cell fate determination in single cell assays of multiply infected bacteria. Whereas the experimental study proposed a "quasi-independent" hypothesis for cell fate determination consistent with an observed data collapse, we demonstrate that observed cell fate results are compatible with an alternative form of data collapse consistent with a partial gene dosage compensation mechanism. We show that including partial gene dosage compensation at the mRNA level in our stochastic model of fate determination leads to the same data collapse observed in the single cell study. Our findings elucidate the importance of transient gene regulatory dynamics in fate determination, and present a novel alternative hypothesis to explain single-cell level heterogeneity within the phage λ lysis-lysogeny decision switch.Richard I JohJoshua S WeitzPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 3, p e1002006 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Richard I Joh Joshua S Weitz To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
description	Cell fate determination is usually described as the result of the stochastic dynamics of gene regulatory networks (GRNs) reaching one of multiple steady-states each of which corresponds to a specific decision. However, the fate of a cell is determined in finite time suggesting the importance of transient dynamics in cellular decision making. Here we consider cellular decision making as resulting from first passage processes of regulatory proteins and examine the effect of transient dynamics within the initial lysis-lysogeny switch of phage λ. Importantly, the fate of an infected cell depends, in part, on the number of coinfecting phages. Using a quantitative model of the phage λ GRN, we find that changes in the likelihood of lysis and lysogeny can be driven by changes in phage co-infection number regardless of whether or not there exists steady-state bistability within the GRN. Furthermore, two GRNs which yield qualitatively distinct steady state behaviors as a function of phage infection number can show similar transient responses, sufficient for alternative cell fate determination. We compare our model results to a recent experimental study of cell fate determination in single cell assays of multiply infected bacteria. Whereas the experimental study proposed a "quasi-independent" hypothesis for cell fate determination consistent with an observed data collapse, we demonstrate that observed cell fate results are compatible with an alternative form of data collapse consistent with a partial gene dosage compensation mechanism. We show that including partial gene dosage compensation at the mRNA level in our stochastic model of fate determination leads to the same data collapse observed in the single cell study. Our findings elucidate the importance of transient gene regulatory dynamics in fate determination, and present a novel alternative hypothesis to explain single-cell level heterogeneity within the phage λ lysis-lysogeny decision switch.
format	article
author	Richard I Joh Joshua S Weitz
author_facet	Richard I Joh Joshua S Weitz
author_sort	Richard I Joh
title	To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
title_short	To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
title_full	To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
title_fullStr	To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
title_full_unstemmed	To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
title_sort	to lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d086a28279b24dd8bcb13a56e4da7da1
work_keys_str_mv	AT richardijoh tolyseornottolysetransientmediatedstochasticfatedeterminationincellsinfectedbybacteriophages AT joshuasweitz tolyseornottolysetransientmediatedstochasticfatedeterminationincellsinfectedbybacteriophages
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To lyse or not to lyse: transient-mediated stochastic fate determination in cells infected by bacteriophages.

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