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Journal ArticleDOI

Multistationarity, the basis of cell differentiation and memory. I. Structural conditions of multistationarity and other nontrivial behavior.

René Thomas, +1 more
- 05 Mar 2001 - 
- Vol. 11, Iss: 1, pp 170-179
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TLDR
The core of the paper is comprised of a formal description of feedback circuits and unions of disjoint circuits, and a normalization of the system versus one of the circuits, which permits an entirely general description in terms of a common diagram in the "circuit space."
Abstract
A biological introduction serves to remind us that differentiation is an epigenetic process, that multistationarity can account for epigenetic differences, including those involved in cell differentiation, and that positive feedback circuits are a necessary condition for multistationarity and, by inference, for differentiation. The core of the paper is comprised of a formal description of feedback circuits and unions of disjoint circuits. We introduce the concepts of full-circuit (a circuit or union of disjoint circuits which involves all the variables of the system), and of ambiguous circuit (a circuit whose sign depends on the location in phase space). We describe the partition of phase space (a) according to the signs of the ambiguous circuits, and (b) according to the signs of the eigenvalues or their real part. We introduce a normalization of the system versus one of the circuits; in two variables, this permits an entirely general description in terms of a common diagram in the “circuit space.” The paper ends with general statements concerning the requirements for multistationarity, stable periodicity, and deterministic chaos.

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Citations
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Journal ArticleDOI

Modeling and simulation of genetic regulatory systems: a literature review.

TL;DR: This paper reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, Boolean networks and their generalizations, ordinary and partial differential equations, qualitative differential equation, stochastic equations, and so on.
Journal ArticleDOI

Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell

TL;DR: This work has demonstrated that molecular regulatory networks can be accurately modeled in mathematical terms and shed light on the design principles of biological control systems and make predictions that have been verified experimentally.
Journal ArticleDOI

Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems

TL;DR: It is shown that for a class of feedback systems of arbitrary order the stability properties of the system can be deduced mathematically from how the system behaves when feedback is blocked, and that this open-loop, feedback-blocked system is guaranteed to be bistable for some range of feedback strengths.
Journal ArticleDOI

A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision

TL;DR: The results explain how a group of intrinsically reversible signal transducers can generate an irreversible response at a systems level, and show how a cell fate can be maintained by a self-sustaining pattern of protein kinase activation.
Journal ArticleDOI

A methodology for the structural and functional analysis of signaling and regulatory networks

TL;DR: This work proposes formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects, and proposes a formalism based on logical interaction hypergraphs, which facilitates a logical steady state analysis (LSSA).
References
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Book

Stability and Complexity in Model Ecosystems

TL;DR: Preface vii Preface to the Second Edition Biology Edition 1.
Journal ArticleDOI

Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs

TL;DR: The role of the nucleus in embryonic differentiation has been the subject of investigations dating back to the beginnings of experimental embryology, and the known cytogenetical mechanisms that could account for nuclear differentiation have been indicated.
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