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Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation

Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent rep...

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Autores principales: Peláez, Nicolás, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R, Katsaggelos, Aggelos K, Amaral, Luís AN, Carthew, Richard W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720516/
https://www.ncbi.nlm.nih.gov/pubmed/26583752
http://dx.doi.org/10.7554/eLife.08924
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author Peláez, Nicolás
Gavalda-Miralles, Arnau
Wang, Bao
Navarro, Heliodoro Tejedor
Gudjonson, Herman
Rebay, Ilaria
Dinner, Aaron R
Katsaggelos, Aggelos K
Amaral, Luís AN
Carthew, Richard W
author_facet Peláez, Nicolás
Gavalda-Miralles, Arnau
Wang, Bao
Navarro, Heliodoro Tejedor
Gudjonson, Herman
Rebay, Ilaria
Dinner, Aaron R
Katsaggelos, Aggelos K
Amaral, Luís AN
Carthew, Richard W
author_sort Peláez, Nicolás
collection PubMed
description Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. Since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction. DOI: http://dx.doi.org/10.7554/eLife.08924.001
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spelling pubmed-47205162016-03-17 Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation Peláez, Nicolás Gavalda-Miralles, Arnau Wang, Bao Navarro, Heliodoro Tejedor Gudjonson, Herman Rebay, Ilaria Dinner, Aaron R Katsaggelos, Aggelos K Amaral, Luís AN Carthew, Richard W eLife Computational and Systems Biology Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. Since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction. DOI: http://dx.doi.org/10.7554/eLife.08924.001 eLife Sciences Publications, Ltd 2015-11-19 /pmc/articles/PMC4720516/ /pubmed/26583752 http://dx.doi.org/10.7554/eLife.08924 Text en © 2015, Peláez et al 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 Computational and Systems Biology
Peláez, Nicolás
Gavalda-Miralles, Arnau
Wang, Bao
Navarro, Heliodoro Tejedor
Gudjonson, Herman
Rebay, Ilaria
Dinner, Aaron R
Katsaggelos, Aggelos K
Amaral, Luís AN
Carthew, Richard W
Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title_full Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title_fullStr Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title_full_unstemmed Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title_short Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
title_sort dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720516/
https://www.ncbi.nlm.nih.gov/pubmed/26583752
http://dx.doi.org/10.7554/eLife.08924
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