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Cell Fate Regulatory Networks

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New Frontiers of Network Analysis in Systems Biology

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Abstract

Cell fate decisions are controlled by intrinsically complex molecular regulatory networks, involving a wide variety of protein–protein and protein-DNA interactions. Due to this complexity, it is difficult to understand molecular regulation of cell fate at the ‘systems’ level. In this chapter we discuss mathematical modeling of cell fate regulatory networks, and explain some ways in which mathematical techniques may be used to elucidate the essential molecular mechanisms that underly cell fate determination. We consider both Boolean networks and ordinary differential equation (ODE) models. We give an illustrative worked example of an ODE model of a simple irreversible molecular switch due to an self-enhancing positive feedback loop and discuss how various commonly-occurring network ‘motifs’ can give rise to certain well-defined dynamics, including switches and oscillators. We conclude with some words on the role of stochasticity in cell fate regulatory networks.

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Notes

  1. 1.

    In fact, from Eq. 2.4 this is always the case for m a positive integer.

  2. 2.

    Note that for γ > 1, B < 0, which physically unrealistic. However, starting from a non-negative initial condition the dynamics are confined to y ≥ 0 since the origin is a nullcline of the system. So, for biologically realistic initial conditions, negative values for the concentration are not obtained.

  3. 3.

    A dynamical system that supports more than one coexisting attractor is said to be multi-stable.

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Acknowledgements

This work was supported by an EPSRC Doctoral Training Centre grant (EP/G03690X/1).

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Authors and Affiliations

  1. Institute for Complex Systems Simulation, School of Mathematics, University of Southampton, University Road, Southampton, SO17 1BJ, UK

    Sonya J. Ridden

  2. Faculty of Medicine and School of Mathematics, Institute for Life Sciences, University of Southampton, Southampton, UK

    Ben D. MacArthur

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  1. Sonya J. Ridden
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Correspondence to Ben D. MacArthur .

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Editors and Affiliations

  1. Pharmacology & Systems Therapeutics, Systems Biology Center New York, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Avi Ma'ayan

  2. Institute For Life Sciences, Southampton University, Highfield Campus, Southampton, SO17 1BJ, United Kingdom

    Ben D. MacArthur

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Ridden, S.J., MacArthur, B.D. (2012). Cell Fate Regulatory Networks. In: Ma'ayan, A., MacArthur, B. (eds) New Frontiers of Network Analysis in Systems Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4330-4_2

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