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Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.

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.

SUBMITTER: Liu X

PROVIDER: S-EPMC3271588 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.

Liu Xinjian X Li Fang F Stubblefield Elizabeth A EA Blanchard Barbara B Richards Toni L TL Larson Gaynor A GA He Yujun Y Huang Qian Q Tan Aik-Choon AC Zhang Dabing D Benke Timothy A TA Sladek John R JR Zahniser Nancy R NR Li Chuan-Yuan CY

Cell research 20111122 2

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 chara ...[more]

PMID: 22105488

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