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Lookup NU author(s): Dr Laura Wadkin, Professor Majlinda LakoORCiD, Professor Nick ParkerORCiD, Professor Anvar ShukurovORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright: © 2021 Wadkin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Human pluripotent stem cells (hPSCs) have the potential to differentiate into all cell types, a property known as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Here we use experimental data of the expression of the pluripotency transcription factor OCT4 in a growing hPSC colony to develop and evaluate mathematical models for temporal pluripotency regulation. We consider fractional Brownian motion and the stochastic logistic equation and explore the effects of both additive and multiplicative noise. We illustrate the use of time-dependent carrying capacities and the introduction of Allee effects to the stochastic logistic equation to describe cell differentiation. We conclude both methods adequately capture the decline in OCT4 upon differentiation, but the Allee effect model has the advantage of allowing differentiation to occur stochastically in a sub-set of cells. This mathematical framework for describing intra-cellular OCT4 regulation can be extended to other transcription factors and developed into predictive models.
Author(s): Wadkin LE, Orozco-Fuentes S, Neganova I, Lako M, Parker NG, Shukurov A
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2021
Volume: 16
Issue: 8
Print publication date: 01/08/2021
Online publication date: 04/08/2021
Acceptance date: 07/07/2021
Date deposited: 23/08/2021
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pone.0254991
DOI: 10.1371/journal.pone.0254991
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