Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3
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 r...
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doaj-689832b5ce1347ec94da084f4ef67ec12020-11-24T21:05:59ZengElsevierStem Cell Research1873-50611876-77532016-09-0117230631710.1016/j.scr.2016.07.004Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3Susanne K. Hansen0Tina C. Stummann1Helena Borland2Lis F. Hasholt3Zeynep Tümer4Jørgen E. Nielsen5Mikkel A. Rasmussen6Troels T. Nielsen7Justus C.A. Daechsel8Karina Fog9Poul Hyttel10Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegårdsvej 7, 1870 Frb C, DenmarkH. Lundbeck A/S, Ottiliavej 9, Valby 2500, DenmarkH. Lundbeck A/S, Ottiliavej 9, Valby 2500, DenmarkInstitute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 N, DenmarkApplied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, Glostrup 2600, DenmarkInstitute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 N, DenmarkDepartment of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegårdsvej 7, 1870 Frb C, DenmarkNeurogenetics Clinic & Research Laboratory, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, DenmarkH. Lundbeck A/S, Ottiliavej 9, Valby 2500, DenmarkH. Lundbeck A/S, Ottiliavej 9, Valby 2500, DenmarkDepartment of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegårdsvej 7, 1870 Frb C, DenmarkThe 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.http://www.sciencedirect.com/science/article/pii/S1873506116300769 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Susanne K. Hansen Tina C. Stummann Helena Borland Lis F. Hasholt Zeynep Tümer Jørgen E. Nielsen Mikkel A. Rasmussen Troels T. Nielsen Justus C.A. Daechsel Karina Fog Poul Hyttel |
spellingShingle |
Susanne K. Hansen Tina C. Stummann Helena Borland Lis F. Hasholt Zeynep Tümer Jørgen E. Nielsen Mikkel A. Rasmussen Troels T. Nielsen Justus C.A. Daechsel Karina Fog Poul Hyttel Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 Stem Cell Research |
author_facet |
Susanne K. Hansen Tina C. Stummann Helena Borland Lis F. Hasholt Zeynep Tümer Jørgen E. Nielsen Mikkel A. Rasmussen Troels T. Nielsen Justus C.A. Daechsel Karina Fog Poul Hyttel |
author_sort |
Susanne K. Hansen |
title |
Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
title_short |
Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
title_full |
Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
title_fullStr |
Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
title_full_unstemmed |
Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
title_sort |
induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3 |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 1876-7753 |
publishDate |
2016-09-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S1873506116300769 |
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