A platform for studies of Huntington’s disease on the basis of induced pluripotent stem cells

Abstract

Huntingtons disease (HD) is one of the most severe hereditaryneurodegenerative disorders caused by CAG repeats expansionin the HTT gene. A recently elaborated technology of geneticreprogramming allows obtaining induced pluripotent stem(iPS) cells from fibroblasts and other differentiated somaticcells. These iPS cells can grow in culture and differentiate inany cell types, including neurons, necessary for studies ofmolecular mechanisms of HD and other neurodegenerativediseases. We obtained, with the use of lentivirus transfection,iPS cells from primary fibroblasts biopsied from three femalepatients with HD (4246 copies of the CAG repeats in themutant allele). The efficiency of reprogramming was approximately0.2%. The embryoid bodies were obtained from someclones of iPS cells, and derivatives of all the three embryo layerswere shown to be formed as a result of spontaneous iPCcells differentiation. At present, our cell lines represent aunique platform for studies of HD. It may be used for establishingan effective system aimed at discoveries of molecularmechanisms undelaying HD and high-throughput search fornovel neuroprotective drugs.

Keywords

• huntington’s disease
• induced pluripotent stem cells
• genetic reprogramming