Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- 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
Published Date
- February 2012
Published In
Volume / Issue
- 22 / 2
Start / End Page
- 321 - 332
PubMed ID
- 22105488
Pubmed Central ID
- PMC3271588
Electronic International Standard Serial Number (EISSN)
- 1748-7838
Digital Object Identifier (DOI)
- 10.1038/cr.2011.181
Language
- eng
Conference Location
- England