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Efficient Differentiation of Mouse Embryonic Stem Cells into Motor Neurons
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p66(ShcA) adaptor molecule accelerates ES cell neural induction.

Evangelia Papadimou1, Alessia Moiana, Donato Goffredo

  • 1Centre for Stem Cell Research and Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milano, Italy.

Molecular and Cellular Neurosciences
|April 24, 2009
PubMed
Summary

The p66 isoform of SHC proteins promotes neural stem cell development. Overexpression of p66ShcA accelerates neural differentiation by influencing the Wnt/beta-catenin pathway in both mouse and human embryonic stem cells.

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Area of Science:

  • Stem cell biology
  • Molecular biology
  • Neuroscience

Background:

  • SHC genes encode adaptor proteins involved in cell division and differentiation.
  • The p66ShcA isoform is linked to longevity and oxidative stress resistance.
  • Previous studies suggest Shc proteins play a role in stem cell processes.

Purpose of the Study:

  • To investigate the role of p66ShcA in embryonic stem cell (ES) neural induction.
  • To determine the effect of p66ShcA on the Wnt/beta-catenin signaling pathway.
  • To assess the conservation of p66ShcA function in human ES cells.

Main Methods:

  • In vitro neural induction of mouse and human ES cells.
  • Overexpression of p66ShcA in ES cells.
  • Analysis of GSK-3beta kinase activation and beta-catenin stabilization.
  • Assessment of beta-catenin transcriptional activity and neuronal differentiation.

Main Results:

  • p66ShcA is upregulated during in vitro neural induction.
  • p66ShcA overexpression reduces GSK-3beta activation and enhances beta-catenin stabilization.
  • Overexpression of p66ShcA accelerates neural induction and neuronal differentiation in mouse ES cells.
  • Similar effects were observed in human ES cells overexpressing p66ShcA.

Conclusions:

  • p66ShcA plays a significant role in modulating the Wnt/beta-catenin pathway.
  • p66ShcA promotes and accelerates neuralization of ES cells.
  • The function of p66ShcA in ES cell neuralization is conserved between mouse and human systems.