Cellular and Molecular Life Sciences

, Volume 73, Issue 21, pp 4085–4100 | Cite as

Modeling simple repeat expansion diseases with iPSC technology

  • Edyta Jaworska
  • Emilia Kozlowska
  • Pawel M. Switonski
  • Wlodzimierz J. KrzyzosiakEmail author


A number of human genetic disorders, including Huntington’s disease, myotonic dystrophy type 1, C9ORF72 form of amyotrophic lateral sclerosis and several spinocerebellar ataxias, are caused by the expansion of various microsatellite sequences in single implicated genes. The neurodegenerative and neuromuscular nature of the repeat expansion disorders considerably limits the access of researchers to appropriate cellular models of these diseases. This limitation, however, can be overcome by the application of induced pluripotent stem cell (iPSC) technology. In this paper, we review the current knowledge on the modeling of repeat expansion diseases with human iPSCs and iPSC-derived cells, focusing on the disease phenotypes recapitulated in these models. In subsequent sections, we provide basic practical knowledge regarding iPSC generation, characterization and differentiation into neurons. We also cover disease modeling in iPSCs, neuronal stem cells and specialized neuronal cultures. Furthermore, we also summarize the therapeutic potential of iPSC technology in repeat expansion diseases.


Pluripotent cells TRED PolyQ diseases Triplet repeat expansion Neurodegeneration Neurons 







Amyotrophic lateral sclerosis


Androgen receptor


Ataxia-telangiectasia mutated protein




Brain-derived neurotrophic factor


Central nervous system


Clustered, regularly interspaced, short, palindromic repeats/Cas9 system


Dopamine- and cAMP-regulated phosphoprotein






Myotonic dystrophy type 1


Dynamin-related protein 1


Dentatorubral-pallidoluysian atrophy


Embryoid body


Epidermal growth factor


Extracellular signal-regulated kinase


Embryonic stem cell


Fuchs endothelial corneal dystrophy


Fibroblast growth factor


Fragile X mental retardation 1


Frontotemporal dementia




Fragile X syndrome


Fragile X associated tremor/ataxia syndrome


Gamma-aminobutyric acid


Homeobox 9


Huntington’s disease


Histone deacetylase






Induced pluripotent stem cell


Krüppel-like factor 4


Microtubule-associated protein 2


Mitogen-activated protein kinase


Mismatch repair system


MutS homolog


Medium spiny neuron


Neural stem cell


Octamer-binding protein 4


Open reading frame


PolyA signals


Protein kinase cAMP




Quantitative PCR


Repeat associated non-AUG translation


RNA binding protein


Spinobulbar muscular atrophy


Spinocerebellar ataxia


Sonic hedgehog


Superoxide dismutase 1


Sex-determining region Y-box 2


Stage-specific embryonic antigen


Transcription activator-like effector nuclease


Untranslated region


Zinc finger nuclease



This work was supported by a Grant from National Science Center (2012/06/A/NZ1/00094 to Wlodzimierz J. Krzyzosiak) and by the Polish Ministry of Science and Higher Education, under the KNOW program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Department of Molecular Biomedicine, Institute of Bioorganic ChemistryPolish Academy of SciencesPoznanPoland

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