Cell reprogramming modelled as transitions in a hierarchy of cell cycles

DOI10.1088/1751-8121/AA89A2zbMATH Open1379.92012arXiv1612.08064OpenAlexW2563625368MaRDI QIDQ4595436FDOQ4595436

Authors: Ryan Hannam, A. Annibale, R. Kühn 

Publication date: 30 November 2017

Published in: Journal of Physics A: Mathematical and Theoretical (Search for Journal in Brave)

Abstract: We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise-induced switching. The former corresponds to a emph{directed} perturbation that induces a transition into a cycle state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g., by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings.

Full work available at URL: https://arxiv.org/abs/1612.08064

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zbMATH Keywords

cell cycleneutral networkcell lineagecell fate decisionscell reprogrammingiPSCspotency hierarchy

Mathematics Subject Classification ID

Neural networks for/in biological studies, artificial life and related topics (92B20) Cell biology (92C37)

Cites Work

• Neural networks and physical systems with emergent collective computational abilities
• Title not available (Why is that?)
• Mean-field analysis of hierarchical associative networks with 'magnetisation'

Cited In (4)

• Percolation in bipartite Boolean networks and its role in sustaining life
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• Cell-type switches induced by stochastic histone modification inheritance
• Mathematical conditions for induced cell differentiation and trans-differentiation in adult cells

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