- Title
- Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes
- Creator
- Mitra, Mitra; Taylor, Paul; Hutchison, Chris; McLeish, T. C. B.; Chakrabarti, Buddapriya
- Date
- 2014
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/170815
- Identifier
- vital:14202
- Identifier
-
https://doi.org/10.1098/rsif.2014.0706
- Identifier
- ISBN: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 howsuch an oscillatory state can provide a framework for understanding more general feedback circuits in cell development. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
- Publisher
- Royal Society of London
- Relation
- Journal of the Royal Society Interface Vol. 11, no. 100 (2014), p.
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright 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.
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- Epigenetics; Gene regulatory networks; Mathematical modelling; Bifurcation (mathematics); Cytology; Delay circuits; Feedback; Genes; Mathematical models; Mathematical transformations; Stem cells; Bifurcation theory; Cell differentiation; Feedback circuits; Oscillatory state; Shape transformation; Sustained oscillations; Time delay; Doxycycline; Autoregulation; Cell maturation; Feedback system; Gene regulatory network; Mathematical model; Oscillation; Somatic cell; Stem cell; Time; Animal; Biological model; Biological rhythm; Genetic epigenesis; Mouse; Physiology; Pluripotent stem cell; Animals; Biological Clocks; Epigenesis, Genetic; Mice; Models, Biological; Pluripotent Stem Cells
- Full Text
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