M. Mitra
Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes
Mitra, M.; Taylor, P.R.; Hutchison, C.J.; McLeish, T.C.B.; Chakrabarti, B.
Authors
P.R. Taylor
C.J. Hutchison
T.C.B. McLeish
B. Chakrabarti
Abstract
The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represent their undifferentiated and differentiated states, respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single-gene regulatory circuit. We show that the interplay of time-dependent drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.
Citation
Mitra, M., Taylor, P., Hutchison, C., McLeish, T., & Chakrabarti, B. (2014). Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes. Journal of the Royal Society. Interface, 11(100), https://doi.org/10.1098/rsif.2014.0706
Journal Article Type | Article |
---|---|
Publication Date | Nov 1, 2014 |
Deposit Date | Jan 14, 2015 |
Publicly Available Date | Jan 19, 2015 |
Journal | Journal of the Royal Society, Interface |
Print ISSN | 1742-5689 |
Electronic ISSN | 1742-5662 |
Publisher | The Royal Society |
Peer Reviewed | Peer Reviewed |
Volume | 11 |
Issue | 100 |
DOI | https://doi.org/10.1098/rsif.2014.0706 |
Keywords | Epigenetics, Mathematical modelling, Gene regulatory networks |
Files
Published Journal Article
(1.2 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
© 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
You might also like
Equilibrium of fluid membranes endowed with orientational order
(2017)
Journal Article
Elasticity dominated surface segregation of small molecules in polymer mixtures
(2016)
Journal Article
Theoretical analysis for the optical deformation of emulsion droplets
(2014)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search