Elucidating the sources of β-catenin dynamics in human neural progenitor cells

PLoS One. 2012;7(8):e42792. doi: 10.1371/journal.pone.0042792. Epub 2012 Aug 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Cell- and Tissue-Based Therapy / methods
  • Computational Biology / methods
  • Computer Simulation
  • Humans
  • Kinetics
  • Models, Statistical
  • Models, Theoretical
  • Neurodegenerative Diseases / therapy
  • Neurons / cytology*
  • Signal Transduction
  • Stem Cells / cytology*
  • Stochastic Processes
  • Time Factors
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism*


  • Wnt Proteins
  • beta Catenin

Grants and funding

This work has been supported as part of the research training group dIEM oSiRiS (The integrative development of modeling and simulation methods for regenerative systems) and the research project dIER MoSiS (Discrete event multi-level modeling and simulation for systems biology), both financed by the German foundation for research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.