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

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 mode...

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Autores principales:	L E Wadkin, S Orozco-Fuentes, I Neganova, M Lako, N G Parker, A Shukurov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1313e2ba3fc47b88c00bf7c595e0340
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spelling	oai:doaj.org-article:b1313e2ba3fc47b88c00bf7c595e03402021-12-02T20:18:44ZA mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.1932-620310.1371/journal.pone.0254991https://doaj.org/article/b1313e2ba3fc47b88c00bf7c595e03402021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254991https://doaj.org/toc/1932-6203Human 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.L E WadkinS Orozco-FuentesI NeganovaM LakoN G ParkerA ShukurovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254991 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L E Wadkin S Orozco-Fuentes I Neganova M Lako N G Parker A Shukurov A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
description	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.
format	article
author	L E Wadkin S Orozco-Fuentes I Neganova M Lako N G Parker A Shukurov
author_facet	L E Wadkin S Orozco-Fuentes I Neganova M Lako N G Parker A Shukurov
author_sort	L E Wadkin
title	A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
title_short	A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
title_full	A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
title_fullStr	A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
title_full_unstemmed	A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
title_sort	mathematical modelling framework for the regulation of intra-cellular oct4 in human pluripotent stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b1313e2ba3fc47b88c00bf7c595e0340
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A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.

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