Abstract
Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1, and Pitx3 can directly and effectively reprogram human fibroblasts into DA neuron-like cells. The reprogrammed cells stained positive for various markers for DA neurons. They also showed characteristic DA uptake and production properties. Moreover, they exhibited DA neuron-specific electrophysiological profiles. Finally, they provided symptomatic relief in a rat PD model. Therefore, our directly reprogrammed DA neuron-like cells are a promising source of cell-replacement therapy for PD.
Original language | English |
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Pages (from-to) | 321-332 |
Number of pages | 12 |
Journal | Cell Research |
Volume | 22 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2012 Feb |
Keywords
- Direct reprogramming
- Dopaminergic neurons
- Fibroblast
- Parkinson's disease
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology