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 | |
| Publication status | Published - 2012 Feb 1 |
| Externally published | Yes |
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Keywords
- Direct reprogramming
- Dopaminergic neurons
- Fibroblast
- Parkinson's disease
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
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
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TY - JOUR
T1 - Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells
AU - Liu, Xinjian
AU - Li, Fang
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
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
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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U2 - 10.1038/cr.2011.181
DO - 10.1038/cr.2011.181
M3 - Article
VL - 22
SP - 321
EP - 332
JO - Cell Research
JF - Cell Research
SN - 1001-0602
IS - 2
ER -