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Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3
- Source :
- Hansen, S K, Stummann, T C, Madsen, H B, Hasholt, L F, Tümer, Z, Nielsen, J E, Rasmussen, M A, Nielsen, T T, Daechsel, J C A, Fog, K & Hyttel, P 2016, ' Induced pluripotent stem cell-derived neurons for the study of spinocerebellar ataxia type 3 ', Stem Cell Research, vol. 17, no. 2, pp. 306-317 . https://doi.org/10.1016/j.scr.2016.07.004, Stem Cell Research, Vol 17, Iss 2, Pp 306-317 (2016)
- Publication Year :
- 2016
-
Abstract
- 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 28days 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.
- Subjects :
- 0301 basic medicine
Synapsin I
congenital, hereditary, and neonatal diseases and abnormalities
Cellular differentiation
Induced Pluripotent Stem Cells
Karyotype
Nerve Tissue Proteins
Biology
Cell Line
03 medical and health sciences
Protein Aggregates
0302 clinical medicine
Neural Stem Cells
medicine
Humans
Induced pluripotent stem cell
Ataxin-3
lcsh:QH301-705.5
Medicine(all)
Genetics
Ionomycin
Glutamate receptor
Brain
Antigens, Nuclear
Cell Differentiation
Cell Biology
General Medicine
Human brain
Machado-Joseph Disease
Fibroblasts
medicine.disease
Cellular Reprogramming
Synapsins
Cell biology
Repressor Proteins
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
nervous system
Microscopy, Fluorescence
Spinocerebellar ataxia
biology.protein
Calcium
NeuN
030217 neurology & neurosurgery
Acetylcholine
Developmental Biology
medicine.drug
Transcription Factors
Subjects
Details
- ISSN :
- 18767753
- Volume :
- 17
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Stem cell research
- Accession number :
- edsair.doi.dedup.....0f24eb2231a1fb81667ab895d53de4d3