西亚试剂：Vitamin C modulates TET1 function during somatic cell repro

Vitamin C modulates TET1 function during somatic cell reprogramming

Jiekai Chen,Lin Guo,Lei Zhang, Haoyu Wu,Jiaqi Yang, He Liu, Xiaoshan Wang,Xiao Hu, Tianpeng Gu,Zhiwei Zhou,  Jing Liu,Jiadong Liu,Hongling Wu,Shi-Qing Mao, Kunlun Mo, Yingying Li, Keyu Lai,Jing Qi,Hongjie Yao,  Guangjin Pan,Guo-Liang Xu & Duanqing Pei

Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs)1 through the activity of histone demethylating dioxygenases2, 3. TET hydroxylases are also dioxygenases implicated in active DNA demethylation4, 5, 6, 7, 8. 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 C2, 9 by modulating the obligatory mesenchymal-to-epithelial transition (MET)10, 11. 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.

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