title: Vitamin C modulates TET1 function during somatic cell reprogramming.
abstract: Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases. TET hydroxylases are also dioxygenases implicated in active DNA demethylation. Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C. TET1 deficiency enhances reprogramming, and its overexpression impairs reprogramming in the context of vitamin C by modulating the obligatory mesenchymal-to-epithelial transition (MET). In the absence of vitamin C, TET1 promotes somatic cell reprogramming independent of MET. Consistently, TET1 regulates 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C-dependent fashion. Our findings suggest that vitamin C has a vital role in determining the biological outcome of TET1 function at the cellular level. Given its benefit to human health, vitamin C should be investigated further for its role in epigenetic regulation.
authors.affiliation: 1] Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. [2] Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. [3].
authors.forename: Jiekai
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Haoyu
authors.initials: H
authors.lastname: Wu
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Yang
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Gu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Jiadong
authors.initials: J
authors.lastname: Liu
authors.forename: Hongling
authors.initials: H
authors.lastname: Wu
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Mao
authors.forename: Kunlun
authors.initials: K
authors.lastname: Mo
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Keyu
authors.initials: K
authors.lastname: Lai
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yao
authors.forename: Guangjin
authors.initials: G
authors.lastname: Pan
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian; D044127:Epigenesis, Genetic / Q000187:drug effects; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse; D001205:Ascorbic Acid