Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3

Research output: Contribution to journalJournal articleResearchpeer-review

Susanne Kofoed Hansen, Tina C. Stummann, Helena Borland Madsen, Lis Frydenreich Hasholt, Zeynep Tümer, Jørgen Erik Nielsen, Mikkel Aabech Rasmussen, Troels Tolstrup Nielsen, Justus C. A. Daechsel, Karina Fog, Poul Hyttel

The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method and the resulting SCA3 iPSCs were differentiated into neurons. These neuronal lines harbored the disease causing mutation, expressed comparable levels of several neuronal markers and responded to the neurotransmitters, glutamate/glycine, GABA and acetylcholine. Additionally, all neuronal cultures formed networks displaying synchronized spontaneous calcium oscillations within 28 days of maturation, and expressed the mature neuronal markers NeuN and Synapsin 1 implying a relatively advanced state of maturity, although not comparable to that of the adult human brain. Interestingly, we were not able to recapitulate the glutamate-induced ataxin-3 aggregation shown in a previously published iPSC-derived SCA3 model. In conclusion, we have generated a panel of SCA3 patient iPSCs and a robust protocol to derive neurons of relatively advanced maturity, which could potentially be valuable for the study of SCA3 disease mechanisms.
Original languageEnglish
JournalStem Cell Research
Issue number2
Pages (from-to)306-317
Number of pages12
Publication statusPublished - Sep 2016

Number of downloads are based on statistics from Google Scholar and

No data available

ID: 171655534