Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells  

作　　者：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 

机构地区：[1]Departments of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA, [2]Shanghai First People's Hospital School of Medicine, Shanghai Jiaotong University, Shanghai 201620, China [3]Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA, [4]Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA [5]Third Military Medical University, Chongqing 400038, China [6]School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China [7]Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA [8]Charles Gates Center for Stem Cell and Regenerative Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA [9]Current address: Department of Dermatology, Box 3135, Duke UniversityMedical Center, Durham, NC 27710, USA

出　　处：《Cell Research》2012年第2期321-332,共12页细胞研究（英文版）

摘　　要：Transplantation of exogenous dopaminergic neuron （DA neurons） is a promising approach for treating Parkin- son＇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 Mashl, Ngn2, Sox2, Nurrl, 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 thera- py for PD.

关 键 词：direct reprogramming dopaminergic neurons FIBROBLAST Parkinson＇s disease 

分 类 号：Q813.11[生物学—生物工程] Q254