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Huntington’s Disease pp 41–73Cite as

Cellular Models: HD Patient-Derived Pluripotent Stem Cells

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

Abstract

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded polyglutamine (polyQ)-encoding repeats in the Huntingtin (HTT) gene. Traditionally, HD cellular models consisted of either patient cells not affected by disease or rodent neurons expressing expanded polyQ repeats in HTT. As these models can be limited in their disease manifestation or proper genetic context, respectively, human HD pluripotent stem cells (PSCs) are currently under investigation as a way to model disease in patient-derived neurons and other neural cell types. This chapter reviews embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) models of disease, including published differentiation paradigms for neurons and their associated phenotypes, as well as current challenges to the field such as validation of the PSCs and PSC-derived cells. Highlighted are potential future technical advances to HD PSC modeling, including transdifferentiation, complex in vitro multiorgan/system reconstruction, and personalized medicine. Using a human HD patient model of the central nervous system, hopefully one day researchers can tease out the consequences of mutant HTT (mHTT) expression on specific cell types within the brain in order to identify and test novel therapies for disease.

Charlene Geater and Sarah Hernandez are co-first authors.

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Acknowledgment

Charlene Geater and Sarah Hernandez contributed equally to this work.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, USA

    Charlene Geater & Leslie Thompson

  2. Sue and Bill Gross Stem Cell Research Center, University of California-Irvine, Irvine, CA, USA

    Charlene Geater, Sarah Hernandez & Leslie Thompson

  3. Department of Neurobiology and Behavior, University of California-Irvine, Irvine, CA, USA

    Sarah Hernandez & Leslie Thompson

  4. Cedars-Sinai Medical Center, Board of Governor’s Regenerative Medicine Institute and Biomedical Sciences, Los Angeles, CA, USA

    Virginia B. Mattis

Authors
  1. Charlene Geater
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  2. Sarah Hernandez
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  3. Leslie Thompson
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  4. Virginia B. Mattis
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Corresponding author

Correspondence to Virginia B. Mattis .

Editor information

Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

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Geater, C., Hernandez, S., Thompson, L., Mattis, V.B. (2018). Cellular Models: HD Patient-Derived Pluripotent Stem Cells. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_4

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  • DOI: https://doi.org/10.1007/978-1-4939-7825-0_4

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