Volume 22, No 2, Feb 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 2, February 2012: 321-332
ORIGINAL ARTICLES
Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells
Xinjian Liu 1,2,*, Fang Li 1,*, Elizabeth A Stubblefield 3,* , Barbara Blanchard 4, Toni L Richards3 , Gaynor A Larson 3, Yujun He 5, Qian Huang 2, Aik-Choon Tan
1Departments of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
2Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, China
3Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
4Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA
5Third Military Medical University, Chongqing 400038, China
6School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China
7Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA
8Charles Gates Center for Stem Cell and Regenerative Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
9Current address: Department of Dermatology, Box 3135, Duke University Medical Center, Durham, NC 27710, USA
Correspondence: Chuan-Yuan Li( Chuan.Li@duke.edu)
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.
10.1038/cr.2011.181; published online 22 November 2011
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