Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell Lineages

Bulletin of Mathematical Biology
Natalia L Komarova, P van den Driessche

Abstract

Design principles of biological networks have been studied extensively in the context of protein-protein interaction networks, metabolic networks, and regulatory (transcriptional) networks. Here we consider regulation networks that occur on larger scales, namely the cell-to-cell signaling networks that connect groups of cells in multicellular organisms. These are the feedback loops that orchestrate the complex dynamics of cell fate decisions and are necessary for the maintenance of homeostasis in stem cell lineages. We focus on "minimal" networks that are those that have the smallest possible numbers of controls. For such minimal networks, the number of controls must be equal to the number of compartments, and the reducibility/irreducibility of the network (whether or not it can be split into smaller independent sub-networks) is defined by a matrix comprised of the cell number increments induced by each of the controlled processes in each of the compartments. Using the formalism of digraphs, we show that in two-compartment lineages, reducible systems must contain two 1-cycles, and irreducible systems one 1-cycle and one 2-cycle; stability follows from the signs of the controls and does not require magnitude restrictions. In thr...Continue Reading

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Citations

Jan 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Dániel GrajzelGergely J Szöllősi
Apr 10, 2020·Royal Society Open Science·Yanli WangChing-Shin Chou
Apr 22, 2018·Bulletin of Mathematical Biology·Alexander R A Anderson, Philip K Maini
Dec 15, 2020·Journal of Theoretical Biology·Ricard Solé, Guim Aguadé-Gorgorió
Aug 25, 2021·Progress in Biophysics and Molecular Biology·Doru Paul, Natalia L Komarova

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