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Testing Three Hypotheses of the Contribution of Geometry and Migration Dynamics to Intestine Crypt Evolution

Araujo, A; Ruebben, A; Bentley, PJ; Basanta, D; (2018) Testing Three Hypotheses of the Contribution of Geometry and Migration Dynamics to Intestine Crypt Evolution. In: Ikegami, T and Virgo, N and Witkowski, O and Oka, M and Suzuki, R and Iizuka, H, (eds.) Artificial Life Conference Proceedings. (pp. pp. 420-427). MIT Press Green open access

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Abstract

Intestinal glands in the small intestine and colon, or intestine crypts, are an important example of tissue homeostasis regulated by the extracellular environment. The crypts are invaginated structures made of a layer of cells that help absorb nutrients from passing food. However, they are continuously worn away by this process and are being continually renovated by stem cells at the bottom of the crypt. These stem cells divide to replace worn cells and may even displace other stem cells so that at a given time the whole crypt becomes monoclonal- a descendant of one single stem cell. From a theoretical standpoint, the time it takes to reach monoclonality is crucial to the understanding of colorectal cancer (CRC) as it offers a key metric for the establishment of cancer initiating mutations; however, the biggest biological contributor to this feature is highly debated. Three key hypotheses have been put forwards, which we investigated with ALife methods. We have abstracted key biological features and modelled them in a bottom-up Agent-Based Model that allowed us to study the biological first principles that rule the fixation of mutations, offering key spatial and temporal understanding of this process. Our results show that the number of basal stem cells have a direct influence on the fixations of mutations and suggesting a lesser role for extracellular influences, while proposing the existence of a threshold to the contribution of cell side displacement.

Type: Proceedings paper
Title: Testing Three Hypotheses of the Contribution of Geometry and Migration Dynamics to Intestine Crypt Evolution
Event: Conference on Artificial Life (ALIFE)
Location: Tokyo, Japan
Dates: 23rd-27th July 2018
Open access status: An open access version is available from UCL Discovery
DOI: doi.org/10.1162/isal_a_00080
Publisher version: https://doi.org/10.1162/isal_a_00080
Language: English
Additional information: © 2018 Massachusetts Institute of Technology Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10087739
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