title: Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming.
abstract: The mechanisms of somatic cell reprogramming have been revealed at multiple levels. However, the lack of tools to monitor different reactive oxygen species (ROS) has left their distinct signals and roles in reprogramming unknown. We hypothesized that mitochondrial flashes (mitoflashes), recently identified spontaneous bursts of mitochondrial superoxide signaling, play a role in reprogramming. Here we show that the frequency of mitoflashes transiently increases, accompanied by flash amplitude reduction, during the early stages of reprogramming. This transient activation of mitoflashes at the early stage enhances reprogramming, whereas sustained activation impairs reprogramming. The reprogramming-promoting function of mitoflashes occurs via the upregulation of Nanog expression that is associated with decreases in the methylation status of the Nanog promoter through Tet2 occupancy. Together our findings provide a previously unknown role for superoxide signaling mediated epigenetic regulation in cell fate determination.
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Ying
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Keshi
authors.initials: K
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Institute of Health Sciences, Anhui University, Heifei 230601, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Linpeng
authors.initials: L
authors.lastname: Li
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Science and Technology of China, Hefei 230027, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Science and Technology of China, Hefei 230027, China.
authors.forename: Deyang
authors.initials: D
authors.lastname: Yao
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Science and Technology of China, Hefei 230027, China.
authors.forename: Feixiang
authors.initials: F
authors.lastname: Bao
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xiang
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and the Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Urology, Cancer Center, Sun Yat-sen University, State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Andrew Paul
authors.initials: AP
authors.lastname: Hutchins
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: liu_xingguo@gibh.ac.cn.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D049308:Dioxygenases; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D000071317:Nanog Homeobox Protein; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D011518:Proto-Oncogene Proteins; D013481:Superoxides; D049308:Dioxygenases; C551914:Tet2 protein, mouse