Cell Mol Life Sci. 2016 Jun 3. [Epub ahead of print]

Modeling simple repeat expansion diseases with iPSC technology.

Jaworska E¹, Kozlowska E¹, Switonski PM¹, Krzyzosiak WJ².

Abstract

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.