A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
02
2021
accepted:
07
07
2021
entrez:
4
8
2021
pubmed:
5
8
2021
medline:
25
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34347824
doi: 10.1371/journal.pone.0254991
pii: PONE-D-21-04839
pmc: PMC8336844
doi:
Substances chimiques
Octamer Transcription Factor-3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0254991Subventions
Organisme : Medical Research Council
ID : G0301182
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I020209/1
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Cell. 2005 Sep 23;122(6):947-56
pubmed: 16153702
Stem Cells. 2005;23(1):124-33
pubmed: 15625129
Acta Biomater. 2013 May;9(5):6369-80
pubmed: 23391989
Mol Cell. 2016 Jun 2;62(5):788-802
pubmed: 27259209
Mol Syst Biol. 2019 Sep;15(9):e9002
pubmed: 31556488
PLoS Comput Biol. 2014 Aug 14;10(8):e1003777
pubmed: 25122140
Stem Cell Res Ther. 2010 Dec 14;1(5):39
pubmed: 21156086
PLoS Comput Biol. 2006 Sep 15;2(9):e123
pubmed: 16978048
Stem Cells. 2007 Feb;25(2):500-10
pubmed: 17068183
PLoS Comput Biol. 2015 Aug 26;11(8):e1004476
pubmed: 26308610
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2075-80
pubmed: 10681449
SN Appl Sci. 2020;2(2):276
pubmed: 32803125
Development. 2014 Jun;141(11):2173-81
pubmed: 24866112
Nat Cell Biol. 2018 Apr;20(4):382-392
pubmed: 29593328
Biochem J. 1913 Oct;7(5):471-80
pubmed: 16742267
Nat Methods. 2014 Aug;11(8):847-54
pubmed: 24973948
Annu Rev Phys Chem. 2007;58:35-55
pubmed: 17037977
Cell Stem Cell. 2012 Apr 6;10(4):440-54
pubmed: 22482508
Development. 2009 Jul;136(14):2311-22
pubmed: 19542351
J Math Biol. 2002 Feb;44(2):150-68
pubmed: 11942530
J Chem Phys. 2018 Feb 14;148(6):064111
pubmed: 29448774
Nat Rev Genet. 2014 Feb;15(2):82-92
pubmed: 24434846
Mol Med Rep. 2017 Nov;16(5):6459-6466
pubmed: 28901500
Cell. 2013 Aug 1;154(3):484-9
pubmed: 23911316
Mol Syst Biol. 2018 Sep 3;14(9):e8140
pubmed: 30177503
PLoS Comput Biol. 2017 Jan 23;13(1):e1005320
pubmed: 28114387
Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):13983-13988
pubmed: 27911801
Nature. 2014 Dec 4;516(7529):56-61
pubmed: 25471879
PLoS One. 2010 Jun 21;5(6):e11238
pubmed: 20574542
Comput Struct Biotechnol J. 2014 Oct 30;12(20-21):14-25
pubmed: 25505503
Phys Biol. 2021 Feb 25;18(2):026003
pubmed: 33296887
Stem Cells Dev. 2006 Dec;15(6):831-7
pubmed: 17253946
Cell. 2013 Nov 7;155(4):869-80
pubmed: 24209624
Nat Rev Mol Cell Biol. 2016 Mar;17(3):194-200
pubmed: 26908143
J Biol Dyn. 2010 Jul;4(4):397-408
pubmed: 22881131
PLoS Biol. 2019 Aug 5;17(8):e3000399
pubmed: 31381560
Front Physiol. 2018 Oct 22;9:1446
pubmed: 30459629
Nat Genet. 2000 Apr;24(4):372-6
pubmed: 10742100
Development. 2015 Jul 1;142(13):2250-60
pubmed: 26130756
Nat Biotechnol. 2002 Dec;20(12):1261-4
pubmed: 12426580
Cell Rep. 2013 Feb 21;3(2):442-57
pubmed: 23375373
PLoS One. 2018 Mar 29;13(3):e0194464
pubmed: 29596533
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
pubmed: 12237400
Stem Cells. 2008 Apr;26(4):903-11
pubmed: 18238855
Sci Rep. 2015 Sep 22;5:14218
pubmed: 26391588
Development. 2014 Jun;141(12):2376-90
pubmed: 24917497
Methods Mol Biol. 2016;1386:331-50
pubmed: 26677190
Cell. 2011 Jun 10;145(6):875-89
pubmed: 21663792
Theor Popul Biol. 2005 Feb;67(1):23-31
pubmed: 15649521