Vitamin C Modulates the Role of TET1 in Somatic Cell Reprogramming
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Time: 2013-11-06
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 dioxygenases implicated in active DNA demethylation. Recently, scientists from Chinese Academy of Sciences (CAS) found that DNA dioxygenase TET1 regulated somatic cell reprogramming depending on the absence of vitamin C.
A research team led by Prof. XU Guoliang, at Shanghai Institute of Biochemistry and Cell Biology (SIBCB), in collaboration with Prof. PEI Duanqing, at the Guangzhou Institutes of Biomedicine and Health (GIBH), CAS, revealed the positive role of TET1 for somatic cell reprogramming, but only in the absence of vitamin C. In the presence of vitamin C, TET1 behaved as a barrier.
TET1 and vitamin C functioned to impede the mesenchymal-to-epithelial transition (MET). Without vitamin C, TET1 facilitated the reprogramming independent of MET. TET1 regulated 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C–dependent fashion. In sum, the results suggested that vitamin C has a vital role in determining the biological outcome of TET1 function. Given the benefit of vitamin C in human health, future work on this micronutrient in epigenetic regulation of both physiological and pathological processes is necessary and promising.
This work entitled “
Vitamin C modulates TET1 function during somatic cell reprogramming” was published online in
Nature Genetics on Oct 27th, 2013. It’ was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Basic Research Program of China, Guangdong Natural Science Funds for Distinguished Young Scholars, the National Natural Science Foundation of China, the Ministry of Science and Technology International Technology Cooperation Program, the Science and Technology Planning Project of Guangdong Province.
Tet1 represses reprogramming in the presence of vitamin C. (a) MEFs with different Tet1 genotype were infected with virus expressing OKS and cultured in iCD1 medium without vitamin C. GFP–positive colonies (expressing GFP from the Pou5f1 (Oct4) promoter) were scored; n = 3 technical replicates. Error bars, s.d. (b) MEFs expressing OKS and inducible TET1 were cultured in iCD1 medium with and without vitamin C. GFP–positive colonies were scored; n = 3 technical replicates. Error bars, s.d. *P < 0.05, **P < 0.01 by two-sided t test. Dox, doxycycline. (c) MEFs expressing OKS and the indicated genes were cultured in iCD1 medium supplemented with increasing concentrations of vitamin C. Control cells received empty vector. GFP–positive colonies were scored; n = 3 technical replicates. Error bars, s.d. Experiments were performed together but are plotted separately, sharing the same control data to avoid overlapping lines. (Image by Dr. XU Guoliang’s group)
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