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Cited by 25Wnt/β-catenin signaling in development and cancerGene Regulatory Network AnalysisDevelopmental Biology and Gene Regulation

Elucidating the Sources of β-Catenin Dynamics in Human Neural Progenitor Cells

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Mazemondet, Orianne, John, Mathias, Leye, Stefan, Rolfs, Arndt, Uhrmacher, Adelinde M.·2012·PLoS ONE
DOI 10.1371/journal.pone.0042792PMC PMC3431164
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Abstract

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.

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Crossref · 10.1371/journal.pone.0042792

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  • Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].

    “Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [46]

    The Introduction describes the study’s later models as extensions of its core model, including versions for cell-cycle asynchrony and self-induced signaling. The Results and Discussion section on self-induced Wnt signaling likewise says the authors extend their model with a Wnt-production reaction. That conflicts with classifying this study’s multiple models as neither extensions nor compositions. (LLM, conf=0.84)

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  • Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57]).

    “Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57])”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [46]

    Materials and Methods, “Parameter estimation & simulation,” reports estimating unknown model parameters, and Results and Discussion describes fitting the model to experimental data. The word “just” overstates the case: the paper also reports sensitivity analysis and investigates stochastic effects, rather than only calibrating its simulations. Page numbers are unavailable in our copy. (LLM, conf=0.83)

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  • In Mazemondet et al. (2012) [46], the core model of the Wnt/β-catenin signaling pathway has been calibrated with wet-lab data from Lee et al. (2003) [28], but this calibrated simulation model was not used and instead, a new calibration with wet-lab data from another study took place.

    “For example, in Mazemondet et al. (2012) [46], the core model of the Wnt/β-catenin signaling pathway has been calibrated with wet-lab data from Lee et al. (2003) [28], but this calibrated simulation model was not used and instead, a new calibration with wet-lab data from another study took place.”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [46]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • An autocrine signaling assumed by Mazemondet et al. (2012) [46] cannot be expressed by SBO.

    “For example, an autocrine signaling assumed by Mazemondet et al. (2012) [46] cannot be expressed by SBO.”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [46]

  • A second cluster forms around the simulation studies [45, 46, 51, 56, 57] and either includes the same wet-lab data from [105, 106], the Cell cycle [46] or ROS [51, 57].

    “A second cluster forms around the simulation studies [45, 46, 51, 56, 57] and either includes the same wet-lab data from [105, 106], the Cell cycle [46] or ROS [51, 57].”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [46]

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Research works printed but not linked: 1

  1. [9]Israsena N, Hu M, Fu W, Kan L, Kessler JA (2004) The presence of FGF2 signaling determines whether beta-catenin exerts effects on proliferation or neuronal differentiation of neural stem cells. Developmental Biology 268: 220– 231. 15031118

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Authors
Mazemondet, O., John, M., Leye, S., Rolfs, A., & Uhrmacher, A. M.
Affiliations
  • University of Rostock (DE)
  • Laboratoire d'Informatique Fondamentale de Lille (FR)
Corresponding author
Uhrmacher, Adelinde M.
ORCID
Uhrmacher, Adelinde M.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-08-20
Volume
7
Issue
8
Pages
e42792
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0042792
PMC
PMC3431164
OpenAlex
W2023332291
Cited by
25
References
63
Citations by year
2025: 1 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 4
FWCI
1.54
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Wnt/β-catenin signaling, human neural progenitor cells, single-cell signaling, neuronal differentiation
MeSH terms
Cell Cycle, Cell Differentiation, Cell Nucleus, Computer Simulation, Humans, Kinetics, Models, Theoretical, Neurons, Stem Cells, Stochastic Processes, Time Factors, Models, Statistical, Signal Transduction, Computational Biology, Neurodegenerative Diseases, Wnt Proteins, beta Catenin, Cell- and Tissue-Based Therapy

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