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Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks

Elucidating the design principles of regulatory networks driving cellular decision-making has fundamental implications in mapping and eventually controlling cell-fate decisions. Despite being complex, these regulatory networks often only give rise to a few phenotypes. Previously, we identified two ‘...

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Autores principales: Hari, Kishore, Ullanat, Varun, Balasubramanian, Archana, Gopalan, Aditi, Jolly, Mohit Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683792/
https://www.ncbi.nlm.nih.gov/pubmed/36269057
http://dx.doi.org/10.7554/eLife.76535
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author Hari, Kishore
Ullanat, Varun
Balasubramanian, Archana
Gopalan, Aditi
Jolly, Mohit Kumar
author_facet Hari, Kishore
Ullanat, Varun
Balasubramanian, Archana
Gopalan, Aditi
Jolly, Mohit Kumar
author_sort Hari, Kishore
collection PubMed
description Elucidating the design principles of regulatory networks driving cellular decision-making has fundamental implications in mapping and eventually controlling cell-fate decisions. Despite being complex, these regulatory networks often only give rise to a few phenotypes. Previously, we identified two ‘teams’ of nodes in a small cell lung cancer regulatory network that constrained the phenotypic repertoire and aligned strongly with the dominant phenotypes obtained from network simulations (Chauhan et al., 2021). However, it remained elusive whether these ‘teams’ exist in other networks, and how do they shape the phenotypic landscape. Here, we demonstrate that five different networks of varying sizes governing epithelial–mesenchymal plasticity comprised of two ‘teams’ of players – one comprised of canonical drivers of epithelial phenotype and the other containing the mesenchymal inducers. These ‘teams’ are specific to the topology of these regulatory networks and orchestrate a bimodal phenotypic landscape with the epithelial and mesenchymal phenotypes being more frequent and dynamically robust to perturbations, relative to the intermediary/hybrid epithelial/mesenchymal ones. Our analysis reveals that network topology alone can contain information about corresponding phenotypic distributions, thus obviating the need to simulate them. We propose ‘teams’ of nodes as a network design principle that can drive cell-fate canalization in diverse decision-making processes.
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spelling pubmed-96837922022-11-24 Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks Hari, Kishore Ullanat, Varun Balasubramanian, Archana Gopalan, Aditi Jolly, Mohit Kumar eLife Computational and Systems Biology Elucidating the design principles of regulatory networks driving cellular decision-making has fundamental implications in mapping and eventually controlling cell-fate decisions. Despite being complex, these regulatory networks often only give rise to a few phenotypes. Previously, we identified two ‘teams’ of nodes in a small cell lung cancer regulatory network that constrained the phenotypic repertoire and aligned strongly with the dominant phenotypes obtained from network simulations (Chauhan et al., 2021). However, it remained elusive whether these ‘teams’ exist in other networks, and how do they shape the phenotypic landscape. Here, we demonstrate that five different networks of varying sizes governing epithelial–mesenchymal plasticity comprised of two ‘teams’ of players – one comprised of canonical drivers of epithelial phenotype and the other containing the mesenchymal inducers. These ‘teams’ are specific to the topology of these regulatory networks and orchestrate a bimodal phenotypic landscape with the epithelial and mesenchymal phenotypes being more frequent and dynamically robust to perturbations, relative to the intermediary/hybrid epithelial/mesenchymal ones. Our analysis reveals that network topology alone can contain information about corresponding phenotypic distributions, thus obviating the need to simulate them. We propose ‘teams’ of nodes as a network design principle that can drive cell-fate canalization in diverse decision-making processes. eLife Sciences Publications, Ltd 2022-10-21 /pmc/articles/PMC9683792/ /pubmed/36269057 http://dx.doi.org/10.7554/eLife.76535 Text en © 2022, Hari et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://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
Hari, Kishore
Ullanat, Varun
Balasubramanian, Archana
Gopalan, Aditi
Jolly, Mohit Kumar
Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title_full Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title_fullStr Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title_full_unstemmed Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title_short Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
title_sort landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683792/
https://www.ncbi.nlm.nih.gov/pubmed/36269057
http://dx.doi.org/10.7554/eLife.76535
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