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

110 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 1

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Keywords

Direct reprogramming
Dopaminergic neurons
Fibroblast
Parkinson's disease

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Cite this

Liu, X., Li, F., Stubblefield, E. A., Blanchard, B., Richards, T. L., Larson, G. A., He, Y., Huang, Q., Tan, A. C., Zhang, D., Benke, T. A., Sladek, J. R., Zahniser, N. R., & Li, C. Y. (2012). Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Research, 22(2), 321-332. https://doi.org/10.1038/cr.2011.181

Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. / Liu, Xinjian; Li, Fang; Stubblefield, Elizabeth A.; Blanchard, Barbara; Richards, Toni L.; Larson, Gaynor A.; He, Yujun; Huang, Qian; Tan, Aik Choon; Zhang, Dabing; Benke, Timothy A.; Sladek, John R.; Zahniser, Nancy R.; Li, Chuan Yuan.

In: Cell Research, Vol. 22, No. 2, 01.02.2012, p. 321-332.

Research output: Contribution to journal › Article

Liu, Xinjian ; Li, Fang ; Stubblefield, Elizabeth A. ; Blanchard, Barbara ; Richards, Toni L. ; Larson, Gaynor A. ; He, Yujun ; Huang, Qian ; Tan, Aik Choon ; Zhang, Dabing ; Benke, Timothy A. ; Sladek, John R. ; Zahniser, Nancy R. ; Li, Chuan Yuan. / Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. In: Cell Research. 2012 ; Vol. 22, No. 2. pp. 321-332.

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Access to Document

10.1038/cr.2011.181