Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

Susanne K Hansen; Helena Borland; Lis F Hasholt; Zeynep Tümer; Jørgen E Nielsen; Mikkel A Rasmussen; Troels T Nielsen; Tina C Stummann; Karina Fog; Poul Hyttel

doi:10.1016/j.scr.2016.02.040

Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

Stem Cell Res. 2016 May;16(3):553-6. doi: 10.1016/j.scr.2016.02.040. Epub 2016 Mar 9.

Authors

Affiliations

¹ Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegårdsvej 7, 1870 Frb C, Denmark; H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.
² H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.
³ Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 N, Denmark.
⁴ Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, Glostrup 2600, Denmark.
⁵ Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 N, Denmark; Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
⁶ Bioneer A/S, Kogle Alle 2, 2970 Hoersholm, Denmark.
⁷ Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
⁸ Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegårdsvej 7, 1870 Frb C, Denmark.

PMID: 27346190
DOI: 10.1016/j.scr.2016.02.040

Abstract

Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs) from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28, SOX2, KLF4, OCT4 and short hairpin RNA targeting P53. The resulting iPSCs had normal karyotype, were free of genomically integrated episomal plasmids, expressed pluripotency markers, could differentiate into the three germ layers in vitro and retained the disease-causing ATXN3 mutation. This iPSC line could be useful for the investigation of SCA3 disease mechanisms.

MeSH terms

Adolescent
Ataxin-3 / genetics
Cell Differentiation
Cells, Cultured
Cellular Reprogramming
Fibroblasts / cytology
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Karyotyping
Kruppel-Like Factor 4
Machado-Joseph Disease / metabolism
Machado-Joseph Disease / pathology*
Male
Plasmids / metabolism
RNA, Small Interfering / metabolism
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Suppressor Protein p53 / antagonists & inhibitors
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

KLF4 protein, human
Kruppel-Like Factor 4
Lin28A protein, human
RNA, Small Interfering
RNA-Binding Proteins
Transcription Factors
Tumor Suppressor Protein p53
Ataxin-3