A multiscale model of epigenetic heterogeneity-driven cell fate decision-making

Author summary Certain modifications of the structure and functioning of the protein/DNA complex called chromatin can allow adult, fully differentiated, cells to adopt a stem cell-like pluripotent state in a purely epigenetic manner, not involving changes in the underlying DNA sequence. Such reprogr...

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Detalhes bibliográficos
Autores: Folguera-Blasco, Núria, Pérez-Carrasco, Rubén, Cuyàs, Elisabet, Menendez, Javier A., Alarcón, Tomàs
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2072/378005
Acesso em linha:http://hdl.handle.net/2072/378005
Access Level:acceso abierto
Palavra-chave:Matemàtiques
51
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spelling A multiscale model of epigenetic heterogeneity-driven cell fate decision-makingFolguera-Blasco, NúriaPérez-Carrasco, RubénCuyàs, ElisabetMenendez, Javier A.Alarcón, TomàsMatemàtiques51Author summary Certain modifications of the structure and functioning of the protein/DNA complex called chromatin can allow adult, fully differentiated, cells to adopt a stem cell-like pluripotent state in a purely epigenetic manner, not involving changes in the underlying DNA sequence. Such reprogramming-like phenomena may constitute an innate reparative route through which human tissues respond to injury and could also serve as a novel regenerative strategy in human pathological situations in which tissue or organ repair is impaired. However, it should be noted that in vivo reprogramming would be capable of maintaining tissue homeostasis provided the acquisition of pluripotency features is strictly transient and accompanied by an accurate replenishment of the specific cell types being lost. Crucially, an excessive reprogramming in the absence of controlled re-differentiation would impair the repair or the replacement of damaged cells, thereby promoting pathological alterations of cell fate. A mechanistic understanding of how the degree of chromatin plasticity dictates the reparative versus pathological behaviour of in vivo reprogramming to rejuvenate aged tissues while preventing tumorigenesis is urgently needed, including especially the intrinsic epigenetic heterogeneity of the tissue resident cells being reprogrammed. We here introduce a novel method that mathematically captures how epigenetic heterogeneity is actually the driving force that governs the routes and kinetics to entry into and exit from a pathological stem-like state. Moreover, our approach computationally validates the likelihood of unlocking chronic, unrestrained plastic states and drive their differentiation down the correct path by solely manipulating the intensity and direction of few epigenetic control switches. Our approach could inspire new therapeutic approaches based on in vivo cell reprogramming for efficient tissue regeneration and rejuvenation and cancer treatment.2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion27 p.application/pdfhttp://hdl.handle.net/2072/378005RECERCAT (Dipòsit de la Recerca de Catalunya)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLOS Computational Biology (Public Library of Science)L'accés als continguts d'aquest document queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons:http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2072/3780052026-05-29T05:05:01Z
dc.title.none.fl_str_mv A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
title A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
spellingShingle A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
Folguera-Blasco, Núria
Matemàtiques
51
title_short A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
title_full A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
title_fullStr A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
title_full_unstemmed A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
title_sort A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
dc.creator.none.fl_str_mv Folguera-Blasco, Núria
Pérez-Carrasco, Rubén
Cuyàs, Elisabet
Menendez, Javier A.
Alarcón, Tomàs
author Folguera-Blasco, Núria
author_facet Folguera-Blasco, Núria
Pérez-Carrasco, Rubén
Cuyàs, Elisabet
Menendez, Javier A.
Alarcón, Tomàs
author_role author
author2 Pérez-Carrasco, Rubén
Cuyàs, Elisabet
Menendez, Javier A.
Alarcón, Tomàs
author2_role author
author
author
author
dc.subject.none.fl_str_mv Matemàtiques
51
topic Matemàtiques
51
description Author summary Certain modifications of the structure and functioning of the protein/DNA complex called chromatin can allow adult, fully differentiated, cells to adopt a stem cell-like pluripotent state in a purely epigenetic manner, not involving changes in the underlying DNA sequence. Such reprogramming-like phenomena may constitute an innate reparative route through which human tissues respond to injury and could also serve as a novel regenerative strategy in human pathological situations in which tissue or organ repair is impaired. However, it should be noted that in vivo reprogramming would be capable of maintaining tissue homeostasis provided the acquisition of pluripotency features is strictly transient and accompanied by an accurate replenishment of the specific cell types being lost. Crucially, an excessive reprogramming in the absence of controlled re-differentiation would impair the repair or the replacement of damaged cells, thereby promoting pathological alterations of cell fate. A mechanistic understanding of how the degree of chromatin plasticity dictates the reparative versus pathological behaviour of in vivo reprogramming to rejuvenate aged tissues while preventing tumorigenesis is urgently needed, including especially the intrinsic epigenetic heterogeneity of the tissue resident cells being reprogrammed. We here introduce a novel method that mathematically captures how epigenetic heterogeneity is actually the driving force that governs the routes and kinetics to entry into and exit from a pathological stem-like state. Moreover, our approach computationally validates the likelihood of unlocking chronic, unrestrained plastic states and drive their differentiation down the correct path by solely manipulating the intensity and direction of few epigenetic control switches. Our approach could inspire new therapeutic approaches based on in vivo cell reprogramming for efficient tissue regeneration and rejuvenation and cancer treatment.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/2072/378005
url http://hdl.handle.net/2072/378005
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLOS Computational Biology (Public Library of Science)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 27 p.
application/pdf
dc.source.none.fl_str_mv RECERCAT (Dipòsit de la Recerca de Catalunya)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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