iPSCs (induced pluripotent stem cells) offer an unparalleled opportunity to generate and study physiologically relevant cell types in culture. iPSCs can be generated by reprogramming almost any somatic cell type using pluripotency factors such as Oct4, SOX2, Nanog and Klf4. By reprogramming cells from patients carrying disease-associated mutations, and subsequent differentiation into the cell type of interest, researchers now have the opportunity to study disease-specific cell types which were previously inaccessible. In the case of PD (Parkinson's disease), reprogramming is advancing rapidly, and cell lines have been generated from patients carrying mutations in several disease-associated genes, including SNCA (α-synuclein), PARK2 (parkin), PINK1 (phosphatase and tensin homologue deleted on chromosome 10-induced putative kinase 1), PARK7 (DJ-1) and LRRK2 (leucine-rich repeat kinase 2), as well as idiopathic cases. Functional dopaminergic neurons have been differentiated from these cells and their physiology has been compared with control neurons. Human dopaminergic neurons had been previously inaccessible until post-mortem, when the disease is generally highly progressed into pathology. In comparison, iPSCs provide a living cell model with the potential to study early molecular changes which accumulate in cells and ultimately result in neurodegeneration. Although clear phenotypes have not yet been unambiguously identified in patient-derived dopaminergic neurons, there are suggested aberrations in cellular pathways involved in neurodegeneration. Overall, these cells offer a unique opportunity to study dopaminergic neurons carrying a ‘Parkinsonian genome’. The present review discusses the advances in cellular reprogramming technologies and studies that have been carried out on PD-derived iPSCs and differentiated dopaminergic neurons.
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October 2012
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Conference Article|
September 19 2012
Cellular reprogramming: a new approach to modelling Parkinson's disease
Elizabeth M. Hartfield;
Elizabeth M. Hartfield
1
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
1To whom correspondence should be addressed (emailelizabeth.hartfield@dpag.ox.ac.uk).
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Hugo J.R. Fernandes;
Hugo J.R. Fernandes
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
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Jane Vowles;
Jane Vowles
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
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Sally A. Cowley;
Sally A. Cowley
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
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Richard Wade-Martins
Richard Wade-Martins
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
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Publisher: Portland Press Ltd
Received:
June 25 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (5): 1152–1157.
Article history
Received:
June 25 2012
Citation
Elizabeth M. Hartfield, Hugo J.R. Fernandes, Jane Vowles, Sally A. Cowley, Richard Wade-Martins; Cellular reprogramming: a new approach to modelling Parkinson's disease. Biochem Soc Trans 1 October 2012; 40 (5): 1152–1157. doi: https://doi.org/10.1042/BST20120159
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