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Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells
Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/[Image: see text]-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 vi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431164/ https://www.ncbi.nlm.nih.gov/pubmed/22952611 http://dx.doi.org/10.1371/journal.pone.0042792 |
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author | Mazemondet, Orianne John, Mathias Leye, Stefan Rolfs, Arndt Uhrmacher, Adelinde M. |
author_facet | Mazemondet, Orianne John, Mathias Leye, Stefan Rolfs, Arndt Uhrmacher, Adelinde M. |
author_sort | Mazemondet, Orianne |
collection | PubMed |
description | Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/[Image: see text]-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/[Image: see text]-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/[Image: see text]-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. |
format | Online Article Text |
id | pubmed-3431164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34311642012-09-05 Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells Mazemondet, Orianne John, Mathias Leye, Stefan Rolfs, Arndt Uhrmacher, Adelinde M. PLoS One Research Article Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/[Image: see text]-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/[Image: see text]-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/[Image: see text]-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. Public Library of Science 2012-08-20 /pmc/articles/PMC3431164/ /pubmed/22952611 http://dx.doi.org/10.1371/journal.pone.0042792 Text en © 2012 Mazemondet et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mazemondet, Orianne John, Mathias Leye, Stefan Rolfs, Arndt Uhrmacher, Adelinde M. Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title | Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title_full | Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title_fullStr | Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title_full_unstemmed | Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title_short | Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells |
title_sort | elucidating the sources of β-catenin dynamics in human neural progenitor cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431164/ https://www.ncbi.nlm.nih.gov/pubmed/22952611 http://dx.doi.org/10.1371/journal.pone.0042792 |
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