A model of sequential branching in hierarchical cell fate determination

DOI10.1016/J.JTBI.2009.07.005zbMATH Open1402.92052arXiv0903.4215OpenAlexW1985607197WikidataQ51811058 ScholiaQ51811058MaRDI QIDQ1625945FDOQ1625945

Authors: D. Foster, Jacob G. Foster, Sui Huang, Stuart A. Kauffman 

Publication date: 26 November 2018

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

Abstract: Multipotent stem or progenitor cells undergo a sequential series of binary fate decisions, which ultimately generate the diversity of differentiated cells. Efforts to understand cell fate control have focused on simple gene regulatory circuits that predict the presence of multiple stable states, bifurcations and switch-like transitions. However, existing gene network models do not explain more complex properties of cell fate dynamics such as the hierarchical branching of developmental paths. Here, we construct a generic minimal model of the genetic regulatory network controlling cell fate determination, which exhibits five elementary characteristics of cell differentiation: stability, directionality, branching, exclusivity, and promiscuous expression. We argue that a modular architecture comprising repeated network elements reproduces these features of differentiation by sequentially repressing selected modules and hence restricting the dynamics to lower dimensional subspaces of the high-dimensional state space. We implement our model both with ordinary differential equations (ODEs), to explore the role of bifurcations in producing the one-way character of differentiation, and with stochastic differential equations (SDEs), to demonstrate the effect of noise on the system. We further argue that binary cell fate decisions are prevalent in cell differentiation due to general features of the underlying dynamical system. This minimal model makes testable predictions about the structural basis for directional, discrete and diversifying cell phenotype development and thus can guide the evaluation of real gene regulatory networks that govern differentiation.

Full work available at URL: https://arxiv.org/abs/0903.4215

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zbMATH Keywords

dynamicsmodularitycell differentiationgenetic regulatory network

Mathematics Subject Classification ID

Systems biology, networks (92C42) Stochastic ordinary differential equations (aspects of stochastic analysis) (60H10) Developmental biology, pattern formation (92C15) Cell biology (92C37)

Cites Work

• Local bifurcation in symmetric coupled cell networks: linear theory
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• High-dimensional switches and the modelling of cellular differentiation
• Rule-Based Modelling, Symmetries, Refinements
• S_N-EQUIVARIANT SYMMETRY-BREAKING BIFURCATIONS
• Towards an understanding of lineage specification in hematopoietic stem cells: a mathematical model for the interaction of transcription factors GATA-1 and PU.1
• A proposal for using the ensemble approach to understand genetic regulatory networks

Cited In (8)

• High-dimensional switches and the modelling of cellular differentiation
• Modelling cell lineage using a meta-Boolean tree model with a relation to gene regulatory networks
• Modeling and visualizing cell type switching
• Denoising of genetic switches based on Parrondo's paradox
• Stochastic and delayed stochastic models of gene expression and regulation
• A framework for state attraction of discrete event systems under partial observation
• Exploring the mechanism of pancreatic cell fate decisions via cell-cell communication
• Cell reprogramming modelled as transitions in a hierarchy of cell cycles

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