Spatio-temporal model of endogenous ROS and raft-dependent WNT/beta-catenin signaling driving cell fate commitment in human neural progenitor cells

PLoS Computational Biology
Fiete HaackAdelinde M Uhrmacher

Abstract

Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-t...Continue Reading

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Citations

Aug 19, 2017·Antioxidants & Redox Signaling·Mauricio Olguín-Albuerne, Julio Morán
Aug 16, 2016·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Arne T Bittig, Adelinde M Uhrmacher
Aug 23, 2019·International Journal of Molecular Medicine·Zhiqiang HeNianlong Yan
Nov 30, 2019·BMC Bioinformatics·Till KösterAdelinde M Uhrmacher
Dec 15, 2016·Frontiers in Pharmacology·Elizabeth J PereiraKevin A Janes
Jun 4, 2018·Cancer Metastasis Reviews·Alfredo Erazo-OliverasRobert S Chapkin
Jul 15, 2020·Journal of Cell Science·Fiete HaackAdelinde M Uhrmacher
Feb 18, 2020·Journal of Cell Communication and Signaling·Gloria RiitanoMaurizio Sorice
May 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhiqiang HeNianlong Yan
Sep 15, 2020·Frontiers in Molecular Neuroscience·Michihiro IgarashiMotohiro Nozumi
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Yagmur AzbazdarGunes Ozhan
May 6, 2021·International Journal of Environmental Research and Public Health·Bernardo Gindri Dos SantosCristiane Matté
Aug 6, 2021·PLoS Computational Biology·Kai BuddeAdelinde M Uhrmacher
Sep 17, 2018·Free Radical Biology & Medicine·Alvaro Martinez GuimeraCarole J Proctor
Sep 7, 2021·Frontiers in Cell and Developmental Biology·Fiete HaackAdelinde M Uhrmacher

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Methods Mentioned

BETA
fluorescence microscopy
Confocal microscopy
electrophoresis

Software Mentioned

Rules
SESSL
Scala
ML
IMAGEJ
JAMES

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