Mitra, M.K., Taylor, P.R., Hutchison, C.J. et al. (2 more authors) (2014) Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes. Interface, 11 (100). 20140706. ISSN 1742-5689
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 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. |
Keywords: | epigenetics; mathematical modelling; gene regulatory networks |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Physics and Astronomy (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Feb 2020 14:15 |
Last Modified: | 04 Feb 2020 14:15 |
Status: | Published |
Publisher: | Royal Society, The |
Refereed: | Yes |
Identification Number: | 10.1098/rsif.2014.0706 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:154995 |