Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells

Xinjian Liu; Fang Li; Elizabeth A. Stubblefield; Barbara Blanchard; Toni L. Richards; Gaynor A. Larson; Yujun He; Qian Huang; Aik Choon Tan; Dabing Zhang; Timothy A. Benke; John R. Sladek; Nancy R. Zahniser; Chuan Yuan Li

doi:10.1038/cr.2011.181

Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells

Xinjian Liu, Fang Li, Elizabeth A. Stubblefield, Barbara Blanchard, Toni L. Richards, Gaynor A. Larson, Yujun He, Qian Huang, Aik Choon Tan, Dabing Zhang, Timothy A. Benke, John R. Sladek, Nancy R. Zahniser, Chuan Yuan Li

Department of Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

138 Citations (Scopus)

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
Pages (from-to)	321-332
Number of pages	12
Journal	Cell Research
Volume	22
Issue number	2
DOIs	https://doi.org/10.1038/cr.2011.181
Publication status	Published - 2012 Feb

Keywords

Direct reprogramming
Dopaminergic neurons
Fibroblast
Parkinson's disease

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/cr.2011.181

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title = "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.",

keywords = "Direct reprogramming, Dopaminergic neurons, Fibroblast, Parkinson's disease",

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year = "2012",

month = feb,

doi = "10.1038/cr.2011.181",

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AU - Stubblefield, Elizabeth A.

AU - Blanchard, Barbara

AU - Richards, Toni L.

AU - Larson, Gaynor A.

AU - He, Yujun

AU - Huang, Qian

AU - Tan, Aik Choon

AU - Zhang, Dabing

AU - Benke, Timothy A.

AU - Sladek, John R.

AU - Zahniser, Nancy R.

AU - Li, Chuan Yuan

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AB - 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.

KW - Direct reprogramming

KW - Dopaminergic neurons

KW - Fibroblast

KW - Parkinson's disease

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Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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