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

Research output: Contribution to journalArticle

103 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 languageEnglish
Pages (from-to)321-332
Number of pages12
JournalCell Research
Volume22
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1
Externally publishedYes

Fingerprint

Dopaminergic Neurons
Fibroblasts
Parkinson Disease
Cell- and Tissue-Based Therapy
Transplantation

Keywords

  • Direct reprogramming
  • Dopaminergic neurons
  • Fibroblast
  • Parkinson's disease

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Liu, X., Li, F., Stubblefield, E. A., Blanchard, B., Richards, T. L., Larson, G. A., ... 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 journalArticle

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, CY 2012, 'Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells', Cell Research, vol. 22, no. 2, pp. 321-332. https://doi.org/10.1038/cr.2011.181
Liu X, Li F, Stubblefield EA, Blanchard B, Richards TL, Larson GA et al. Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Research. 2012 Feb 1;22(2):321-332. https://doi.org/10.1038/cr.2011.181
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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