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Orianne Mazemondet, Mathias John, Stefan Leye, Arndt Rolfs, and Adelinde M Uhrmacher (2012)

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

PLOS-One, 7(8):1-12.

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 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 heterogeneously distributed w.r.t. to their cell cycle states. Therefore, we derive a model on 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 is negligible. We then further extend our model in a way that allows us to provide additional evidence that self-induced Wnt signaling occurs in RVM cells. All our investigations are performed within the stochastic realm. We report on signicant stochastic effects that directly result from model parameters provided in literature and contradict with experimental observations.

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