Cellular Models: HD Patient-Derived Pluripotent Stem Cells

  • Charlene Geater
  • Sarah Hernandez
  • Leslie Thompson
  • Virginia B. MattisEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1780)


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.


Huntington’s disease (HD) Huntingtin (HTT) Induced pluripotent stem cell (iPSC) Embryonic stem cell (ESC) Striatum Modeling Differentiation 



Charlene Geater and Sarah Hernandez contributed equally to this work.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Charlene Geater
    • 1
    • 2
  • Sarah Hernandez
    • 2
    • 3
  • Leslie Thompson
    • 1
    • 2
    • 3
  • Virginia B. Mattis
    • 4
    Email author
  1. 1.Department of Psychiatry and Human BehaviorUniversity of California-IrvineIrvineUSA
  2. 2.Sue and Bill Gross Stem Cell Research CenterUniversity of California-IrvineIrvineUSA
  3. 3.Department of Neurobiology and BehaviorUniversity of California-IrvineIrvineUSA
  4. 4.Cedars-Sinai Medical CenterBoard of Governor’s Regenerative Medicine Institute and Biomedical SciencesLos AngelesUSA

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