Vitamin C modulates TET1 function during somatic cell reprogramming

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

doi:10.1038/ng.2807

Cited by 280 publications

(234 citation statements)

References 36 publications

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“…Previous studies have reported the proliferative and reprogramming effects of vitamin C on stem cells [36][37][38]; however, the molecular mechanism underlying vitamin C-induced stem cell stimulation has not been fully elucidated. Here, we demonstrated that vitamin C induces the proliferation, and vitamin C preconditioning enhanced the hair-regenerative potential of ASCs.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Kim

Sung

et al. 2014

Stem Cells and Development

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Although adipose-derived stem cells (ASCs) show promise for cell therapy, there is a tremendous need for developing ASC activators. In the present study, we investigated whether or not vitamin C increases the survival, proliferation, and hair-regenerative potential of ASCs. In addition, we tried to find the molecular mechanisms underlying the vitamin C-mediated stimulation of ASCs. Sodium-dependent vitamin C transporter 2 (SVCT2) is expressed in ASCs, and mediates uptake of vitamin C into ASCs. Vitamin C increased the survival and proliferation of ASCs in a dose-dependent manner. Vitamin C increased ERK1/2 phosphorylation, and inhibition of the mitogen-activated protein kinase (MAPK) pathway attenuated the proliferation of ASCs. Microarray and quantitative polymerase chain reaction showed that vitamin C primarily upregulated expression of proliferation-related genes, including Fos, E2F2, Ier2, Mybl1, Cdc45, JunB, FosB, and Cdca5, whereas Fos knock-down using siRNA significantly decreased vitamin C-mediated ASC proliferation. In addition, vitamin C-treated ASCs accelerated the telogen-to-anagen transition in C 3 H/HeN mice, and conditioned medium from vitamin C-treated ASCs increased the hair length and the Ki 67 -positive matrix keratinocytes in hair organ culture. Vitamin C increased the mRNA expression of HGF, IGFBP6, VEGF, bFGF, and KGF, which may mediate hair growth promotion. In summary, vitamin C is transported via SVCT2, and increased ASC proliferation is mediated by the MAPK pathway. In addition, vitamin C preconditioning enhanced the hair growth promoting effect of ASCs. Because vitamin C is safe and effective, it could be used to increase the yield and regenerative potential of ASCs.

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Section: Discussionmentioning

confidence: 99%

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Kim

Sung

et al. 2014

Stem Cells and Development

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“…Conversely, TET1 overexpression impairs reprogramming (76). Although TET1 in the absence of ascorbate remains functional, the addition of ascorbate is critical for the epithelial-tomesenchymal transition during reprogramming to pluripotency (79).…”

Section: Ascorbatementioning

confidence: 99%

Metabolism in pluripotency: Both driver and passenger?

Dahan

Nguyen

et al. 2019

Journal of Biological Chemistry

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Downloaded from2 Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or "passenger" of cell fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development.Most investigators view metabolism, which encompasses the synthesis and utilization of macromolecules and energy, as a passive supporter of self-renewal and rapid proliferation in pluripotent stem cells (PSCs) 1 and their differentiated, slower dividing progeny. However, exciting recent studies are changing this perception by showing an active role for metabolism in PSC fate determination.

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“…This antioxidant promotes TET enzyme-mediated DNA demethylation and acts as a co-factor for histone demethylases JHDM1A/1B in ESCs Chen et al, 2013b;Esteban et al, 2010;Stadtfeld et al, 2012;Wang et al, 2011a). This finding is in line with the emerging importance of metabolic regulation in ESCs (Shyh-Chang et al, 2013a).…”

Section: Oxygen and Nutrients Mediate Epigenetic Dynamicsmentioning

confidence: 99%

Chromatin features and the epigenetic regulation of pluripotency states in ESCs

Tee

Reinberg

2014

Development

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In pluripotent stem cells, the interplay between signaling cues, epigenetic regulators and transcription factors orchestrates developmental potency. Flexibility in gene expression control is imparted by molecular changes to the nucleosomes, the building block of chromatin. Here, we review the current understanding of the role of chromatin as a plastic and integrative platform to direct gene expression changes in pluripotent stem cells, giving rise to distinct pluripotent states. We will further explore the concept of epigenetic asymmetry, focusing primarily on histone stoichiometry and their associated modifications, that is apparent at both the nucleosome and chromosome-wide levels, and discuss the emerging importance of these asymmetric chromatin configurations in diversifying epigenetic states and their implications for cell fate control.

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Vitamin C modulates TET1 function during somatic cell reprogramming

Cited by 280 publications

References 36 publications

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Metabolism in pluripotency: Both driver and passenger?

Chromatin features and the epigenetic regulation of pluripotency states in ESCs

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