Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.
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.
Liu, X; Li, F; Stubblefield, EA; Blanchard, B; Richards, TL; Larson, GA; He, Y; Huang, Q; Tan, A-C; Zhang, D; Benke, TA; Sladek, JR; Zahniser, NR; Li, C-Y
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