Nov 25, 2013

Investigating the relation between stochastic differentiation and homeostasis in intestinal crypts via multiscale modeling

BioRxiv : the Preprint Server for Biology
Alex GraudenziMarco Antoniotti

Abstract

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 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 maintenance and clona...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Patterns
Displacement - Action
Genes
TAL1
Cell to Cell Adhesion Signaling Pathway
Biologic Development
Colorectal Neoplasms
Organ
Cell Differentiation Process

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