Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.

Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still only p...

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Autores principales:	Alex Graudenzi, Giulio Caravagna, Giovanni De Matteis, Marco Antoniotti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e97e3feb177c44e7af2bf0508b8a02cf
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spelling	oai:doaj.org-article:e97e3feb177c44e7af2bf0508b8a02cf2021-11-18T08:18:01ZInvestigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.1932-620310.1371/journal.pone.0097272https://doaj.org/article/e97e3feb177c44e7af2bf0508b8a02cf2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24869488/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still only partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of biological noise. We show that this modeling approach captures the major dynamical phenomena that characterize the regular physiology of crypts, such as cell sorting, coordinate migration, dynamic turnover, stem cell niche correct positioning and clonal expansion. All in all, the model suggests that the process of stochastic differentiation might be sufficient to drive the crypt to homeostasis, under certain crypt configurations. Besides, our approach allows to make precise quantitative inferences that, when possible, were matched to the current biological knowledge and it permits to investigate the role of gene-level perturbations, with reference to cancer development. We also remark the theoretical framework is general and may be applied to different tissues, organs or organisms.Alex GraudenziGiulio CaravagnaGiovanni De MatteisMarco AntoniottiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97272 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alex Graudenzi Giulio Caravagna Giovanni De Matteis Marco Antoniotti Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
description	Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still only partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of biological noise. We show that this modeling approach captures the major dynamical phenomena that characterize the regular physiology of crypts, such as cell sorting, coordinate migration, dynamic turnover, stem cell niche correct positioning and clonal expansion. All in all, the model suggests that the process of stochastic differentiation might be sufficient to drive the crypt to homeostasis, under certain crypt configurations. Besides, our approach allows to make precise quantitative inferences that, when possible, were matched to the current biological knowledge and it permits to investigate the role of gene-level perturbations, with reference to cancer development. We also remark the theoretical framework is general and may be applied to different tissues, organs or organisms.
format	article
author	Alex Graudenzi Giulio Caravagna Giovanni De Matteis Marco Antoniotti
author_facet	Alex Graudenzi Giulio Caravagna Giovanni De Matteis Marco Antoniotti
author_sort	Alex Graudenzi
title	Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
title_short	Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
title_full	Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
title_fullStr	Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
title_full_unstemmed	Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
title_sort	investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e97e3feb177c44e7af2bf0508b8a02cf
work_keys_str_mv	AT alexgraudenzi investigatingtherelationbetweenstochasticdifferentiationhomeostasisandclonalexpansioninintestinalcryptsviamultiscalemodeling AT giuliocaravagna investigatingtherelationbetweenstochasticdifferentiationhomeostasisandclonalexpansioninintestinalcryptsviamultiscalemodeling AT giovannidematteis investigatingtherelationbetweenstochasticdifferentiationhomeostasisandclonalexpansioninintestinalcryptsviamultiscalemodeling AT marcoantoniotti investigatingtherelationbetweenstochasticdifferentiationhomeostasisandclonalexpansioninintestinalcryptsviamultiscalemodeling
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Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.

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