title: Tet3-Mediated DNA Demethylation Contributes to the Direct Conversion of Fibroblast to Functional Neuron.
abstract: The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN). Gene expression profiles demonstrate distinct neuron-specific gene clusters in iNs compared with primary neurons. Induced neurons display maturing firing patterns and form functional synapses. Additionally, we observe that the level of 5hmC in iNs gradually increases during the time course of transdifferentiation. These findings suggest that DNA demethylation may regulate direct lineage commitment, representing an avenue for investigating the process of transdifferentiation.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China; Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish Center for Education and Research, Beijing 100190, China.
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China; Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish Center for Education and Research, Beijing 100190, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zixiao
authors.initials: Z
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tongbiao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Baoyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: jwjiao@ioz.ac.cn.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D049308:Dioxygenases; D055724:Electrophysiological Phenomena; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D049308:Dioxygenases; C551915:Tet3 protein, mouse
keywords: DNA demethylation; Tet3; conversion; fibroblast; iN cell; induction; neuron; trans-differentiation