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...

Full description

Bibliographic Details
Main Authors: L E Wadkin, S Orozco-Fuentes, I Neganova, M Lako, N G Parker, A Shukurov
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0254991
id doaj-b1313e2ba3fc47b88c00bf7c595e0340
record_format Article
spelling doaj-b1313e2ba3fc47b88c00bf7c595e03402021-08-10T04:30:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01168e025499110.1371/journal.pone.0254991A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.L E WadkinS Orozco-FuentesI NeganovaM LakoN G ParkerA ShukurovHuman 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.https://doi.org/10.1371/journal.pone.0254991
collection DOAJ
language English
format Article
sources DOAJ
author L E Wadkin
S Orozco-Fuentes
I Neganova
M Lako
N G Parker
A Shukurov
spellingShingle 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.
PLoS ONE
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)
series PLoS ONE
issn 1932-6203
publishDate 2021-01-01
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.
url https://doi.org/10.1371/journal.pone.0254991
work_keys_str_mv AT lewadkin amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT sorozcofuentes amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ineganova amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT mlako amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ngparker amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ashukurov amathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT lewadkin mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT sorozcofuentes mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ineganova mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT mlako mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ngparker mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
AT ashukurov mathematicalmodellingframeworkfortheregulationofintracellularoct4inhumanpluripotentstemcells
_version_ 1721212919278993408