Mazemondet2012 - beta-catenin dynamics in human neural progenitor cells

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  • Elucidating the sources of β-catenin dynamics in human neural progenitor cells.
  • Mazemondet O, John M, Leye S, Rolfs A, Uhrmacher AM
  • PloS one , 0/ 2012 , Volume 7 , pages: e42792 , PubMed ID: 22952611
  • Modelling and Simulation Group, Institute of Computer Science, University of Rostock, Rostock, Germany.
  • Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/β-catenin signaling pathway is known to be involved in the differentiation process of hNPCs. RVM cells form a common cell model of hNPCs for in vitro investigation. Previous observations in RVM cells raise the question of whether observed kinetics of the Wnt/β-catenin pathway in later differentiation phases are subject to self-induced signaling. However, a concern when investigating RVM cells is that experimental results are possibly biased by the asynchrony of cells w.r.t. the cell cycle. In this paper, we present, based on experimental data, a computational modeling study on the Wnt/β-catenin signaling pathway in RVM cell populations asynchronously distributed w.r.t. to their cell cycle phases. Therefore, we derive a stochastic model of the pathway in single cells from the reference model in literature and extend it by means of cell populations and cell cycle asynchrony. Based on this, we show that the impact of the cell cycle asynchrony on wet-lab results that average over cell populations is negligible. We then further extend our model and the thus-obtained simulation results provide additional evidence that self-induced Wnt signaling occurs in RVM cells. We further report on significant stochastic effects that directly result from model parameters provided in literature and contradict experimental observations.
Submitter of the first revision: Orianne Mazemondet
Submitter of this revision: Orianne Mazemondet
Modellers: Orianne Mazemondet

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is (1 statement)
BioModels Database MODEL1303140000

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Taxonomy Homo sapiens

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Mathematical Modelling Ontology Ordinary differential equation model

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Brenda Tissue Ontology midbrain

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  • Model originally submitted by : Orianne Mazemondet
  • Submitted: Mar 14, 2013 3:03:57 PM
  • Last Modified: Mar 15, 2013 1:30:36 PM
  • Version: 2 public model Download this version
    • Submitted on: Mar 15, 2013 1:30:36 PM
    • Submitted by: Orianne Mazemondet
    • With comment: Current version of Mazemondet2012 - beta-catenin dynamics in human neural progenitor cells
  • Version: 1 public model Download this version
    • Submitted on: Mar 14, 2013 3:03:57 PM
    • Submitted by: Orianne Mazemondet
    • With comment: Original import of New Model

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