title: Chemical conversion of mouse fibroblasts into functional dopaminergic neurons.
abstract: Ectopic expression of lineage-specific transcription factors facilitates the conversion of mammalian somatic cells into dopaminergic (DA) neurons, which is a promising strategy for cell therapy of Parkinson's disease (PD). However, this approach still has some drawbacks limiting its clinical application due to the potential risks of integrating vectors into the host genome. Therefore, it is critical to seek a more desired approach to generate DA neurons derived from mammalian somatic cells. Here, we report that mouse embryonic fibroblasts (MEFs) can be efficiently converted into DA neurons by using small molecules along with specific growth factors. These neuron-like cells generate DA neuronal morphology, and acquire immunocytochemical and calcium imaging special for neuronal electrophysiological profile. More importantly, these converted cells can secrete dopamine, indicating that they are functionally similar to DA neurons. Taken together, our study might provide a promising cell source for treating PD by using chemical approach without introduction of exogenous transcription factors.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China. Electronic address: quxuhm123@163.com.
authors.forename: Huiming
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China; Collaborative Innovative Research Center for Systems Biomedicine, Shanghai, China. Electronic address: gao.weiqiang@sjtu.edu.cn.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D054852:Small Molecule Libraries
keywords: Chemical; Conversion; Dopaminergic neuron; Fibroblasts