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Phenotypic Screening Using Mouse and Human Stem Cell-Based Models of Neuroinflammation and Gene Expression Analysis to Study Drug Responses

  • Masin Abo-Rady
  • Jessica Bellmann
  • Michael Glatza
  • Lara Marrone
  • Lydia Reinhardt
  • Santiago Tena
  • Jared Sterneckert
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1888)

Abstract

High-throughput phenotypic screening enables the identification of new therapeutic targets even when the molecular mechanism underlying the disease is unknown. In the case of neurodegenerative disease, there is a dire need to identify new targets that can ameliorate, halt, or reverse degeneration. Stem cell-based disease models are particularly powerful tools for phenotypic screening because they use the same cell type affected in patients. Here, we describe the expansion of mouse stem cells and human induced pluripotent stem cells as well as the differentiation of these cells into neural lineages that, when exposed to neuroinflammatory stress, can be used for compound screening followed by hit identification, validation, and target deconvolution.

Key words

Pluripotent stem cells Disease modelling Phenotypic screening Neurodegeneration Neuroinflammation Neuronal differentiation Target deconvolution 

Notes

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft, EU Joint Programme–Neurodegenerative Disease Research, the Bundesministerium für Bildung und Forschung, and the Max Planck Society. J.B., M.G., and L.M. are supported by fellowships from the Hans and Ilse Breuer Stiftung. We thank Tanya Levin for editing the manuscript.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Masin Abo-Rady
    • 1
  • Jessica Bellmann
    • 1
  • Michael Glatza
    • 2
  • Lara Marrone
    • 1
  • Lydia Reinhardt
    • 1
    • 2
  • Santiago Tena
    • 1
  • Jared Sterneckert
    • 1
  1. 1.Center for Regenerative Therapies Dresden (CRTD)Technische Universität DresdenDresdenGermany
  2. 2.Department of Cell and Developmental BiologyMax Planck Institute for Molecular BiomedicineMünsterGermany

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