YAC128 mouse model-derived iPSCs show markers of Huntington disease

• Autorzy: Szlachcic W.J. , Switonski P. M. , Krzyzosiak W. J. , Figiel M.
• Języki publikacji: EN

Abstrakty

EN

Huntington disease (HD) is an incurable brain disorder caused by expansion of CAG repeats in a HTT gene resulting in toxic huntingtin with long polyglutamine tract. In HD, neurons die in cerebral cortex and striatum and therefore a treatment option is a cell therapy using cells generated from induced pluripotent stem cells (iPSC) from patients. We have established a model of such therapy comprising iPSCs lines from the adult dermal fibroblasts of YAC128 HD mouse model. The cells were reprogrammed using transposable and excisable piggyBac vector expressing OSKML transcription factors. These iPSC cells show pluripotency both in in vitro (Tuj-positive neurons and beating cardiomiocytes) and in vivo (teratoma formation) differentiation assays, thus being suitable for experimental cell therapy. In addition, our YAC128/iPSC show alterations of Wnt/β-catenin and MAPK signaling pathways probably resulting from expression of human mutant huntingtin. Thus, cells suitable for cell therapy would need silencing of the mutant huntingtin. Therefore we have generated a series of therapeutic constructs based on piggyBac transposon expressing anti-huntingtin siRNAs in sh-miR backbone. We show that the construct when integrated into iPSC genome efficiently silences mutant huntingtin expression. Our platform is a useful model for investigating cell therapy outcomes in the HD mouse model.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: Suppl.1
• Opis fizyczny: p.57

Twórcy

autor

Szlachcic W.J.

• Laboratory of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

autor

Switonski P. M.

• Laboratory of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

autor

Krzyzosiak W. J.

• Laboratory of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

autor

Figiel M.

• Laboratory of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland