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Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes

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Title Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes
 
Creator MITRA, MK
TAYLOR, PR
HUTCHISON, CJ
MCLEISH, TCB
CHAKRABARTI, B
 
Subject epigenetics
mathematical modelling
gene regulatory networks
PLURIPOTENT STEM-CELLS
SOMATIC-CELLS
FIBROBLASTS
EXPRESSION
MOUSE
DIFFERENTIATION
BISTABILITY
 
Description 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 non-linear 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.
 
Publisher ROYAL SOC
 
Date 2014-12-28T14:56:53Z
2014-12-28T14:56:53Z
2014
 
Type Article
 
Identifier JOURNAL OF THE ROYAL SOCIETY INTERFACE, 11(100)
1742-5689
1742-5662
http://dx.doi.org/10.1098/rsif.2014.0706
http://dspace.library.iitb.ac.in/jspui/handle/100/16810
 
Language English