title: Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.
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.
authors: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Xinjian
authors: X
authors: Liu
authors: Fang
authors: F
authors: Li
authors: Elizabeth A
authors: EA
authors: Stubblefield
authors: Barbara
authors: B
authors: Blanchard
authors: Toni L
authors: TL
authors: Richards
authors: Gaynor A
authors: GA
authors: Larson
authors: Yujun
authors: Y
authors: He
authors: Qian
authors: Q
authors: Huang
authors: Aik-Choon
authors: AC
authors: Tan
authors: Dabing
authors: D
authors: Zhang
authors: Timothy A
authors: TA
authors: Benke
authors: John R
authors: JR
authors: Sladek
authors: Nancy R
authors: NR
authors: Zahniser
authors: Chuan-Yuan
authors: CY
authors: Li
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000637:transplantation; D005347:Fibroblasts / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004298:Dopamine; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C065500:ASCL1 protein, human; C491183:NEUROG2 protein, human; C433629:homeobox protein PITX3