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A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

Lookup NU author(s): Dr Laura Wadkin, Professor Majlinda Lako, Dr Nick Parker, Professor Anvar Shukurov

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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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