Ascorbic acid in epigenetic reprogramming

2021 ◽  
Vol 16 ◽  
Author(s):  
Xinhui Liu ◽  
Aamir Khan ◽  
Huan Li ◽  
Shensen Wang ◽  
Xuechai Chen ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Somatic Cell ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Cellular Reprogramming ◽  
Epigenetic Reprogramming ◽  
Cell Reprogramming ◽  
Histone Demethylases ◽  
Somatic Cell Reprogramming

: Emerging evidence suggests that ascorbic acid (vitamin C) enhances the reprogramming process by multiple mechanisms. This is primarily due to its cofactor role in Fe(II) and 2-oxoglutarate-dependent dioxygenases, including the DNA demethylases Ten Eleven Translocase (TET) and histone demethylases. Epigenetic variations have been shown to play a critical role in somatic cell reprogramming. DNA methylation and histone methylation are extensively recognized as barriers to somatic cell reprogramming. N6-methyladenosine (m6A), known as RNA methylation, is an epigenetic modification of mRNAs and has also been shown to play a role in regulating cellular reprogramming. Multiple cofactors are reported to promote the activity of demethylases, including vitamin C. This review focuses on examining the evidence and mechanism of vitamin C in DNA and histone demethylation and highlights its potential involvement in regulating m6A demethylation. It also shows the significant contribution of vitamin C in epigenetic regulation and the affiliation of demethylases with vitamin C-facilitated epigenetic reprogramming.

scholarly journals The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner

2011 ◽  
Vol 9 (6) ◽  
pp. 575-587 ◽  
Author(s):  
Tao Wang ◽  
Keshi Chen ◽  
Xiaoming Zeng ◽  
Jianguo Yang ◽  
Yun Wu ◽  
...  
Keyword(s):  
Vitamin C ◽  
Somatic Cell ◽  
Cell Reprogramming ◽  
Dependent Manner ◽  
Histone Demethylases ◽  
Somatic Cell Reprogramming

scholarly journals Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming

2019 ◽  
Vol 33 (12) ◽  
pp. 13982-13997 ◽  
Author(s):  
Lei Yang ◽  
Xuefei Liu ◽  
Lishuang Song ◽  
Guanghua Su ◽  
Anqi Di ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Epigenetic Modification ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming

scholarly journals AKT signaling is associated with epigenetic reprogramming via the upregulation of TET and its cofactor, alpha-ketoglutarate during iPSC generation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yoichi Sekita ◽  
Yuki Sugiura ◽  
Akari Matsumoto ◽  
Yuki Kawasaki ◽  
Kazuya Akasaka ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Primordial Germ Cells ◽  
Akt Signaling ◽  
Dna Demethylation ◽  
Cellular Reprogramming ◽  
Epigenetic Reprogramming ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming ◽  
A Genome ◽  
Ipsc Generation

Abstract Background Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival and tumorigenesis. The activation of AKT signaling promotes the cellular reprogramming including generation of induced pluripotent stem cells (iPSCs) and dedifferentiation of primordial germ cells (PGCs). Previous studies suggested that AKT promotes reprogramming by activating proliferation and glycolysis. Here we report a line of evidence that supports the notion that AKT signaling is involved in TET-mediated DNA demethylation during iPSC induction. Methods AKT signaling was activated in mouse embryonic fibroblasts (MEFs) that were transduced with OCT4, SOX2 and KLF4. Multiomics analyses were conducted in this system to examine the effects of AKT activation on cells undergoing reprogramming. Results We revealed that cells undergoing reprogramming with artificially activated AKT exhibit enhanced anabolic glucose metabolism and accordingly increased level of cytosolic α-ketoglutarate (αKG), which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET is upregulated. Consistent with the upregulation of αKG production and TET, we observed a genome-wide increase in 5-hydroxymethylcytosine (5hmC), which is an intermediate in DNA demethylation. Moreover, the DNA methylation level of ES-cell super-enhancers of pluripotency-related genes is significantly decreased, leading to the upregulation of associated genes. Finally, the transduction of TET and the administration of cell-permeable αKG to somatic cells synergistically enhance cell reprogramming by Yamanaka factors. Conclusion These results suggest the possibility that the activation of AKT during somatic cell reprogramming promotes epigenetic reprogramming through the hyperactivation of TET at the transcriptional and catalytic levels.

scholarly journals Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2

Nature ◽  
2012 ◽  
Vol 488 (7413) ◽  
pp. 652-655 ◽  
Author(s):  
Claudia A. Doege ◽  
Keiichi Inoue ◽  
Toru Yamashita ◽  
David B. Rhee ◽  
Skylar Travis ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Early Stage ◽  
Epigenetic Modification ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming

Vitamin C improves the quality of somatic cell reprogramming

2012 ◽  
Vol 44 (4) ◽  
pp. 366-367 ◽  
Author(s):  
Miguel A Esteban ◽  
Duanqing Pei
Keyword(s):  
Vitamin C ◽  
Somatic Cell ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming

Vitamin C modulates TET1 function during somatic cell reprogramming

2013 ◽  
Vol 45 (12) ◽  
pp. 1504-1509 ◽  
Author(s):  
Jiekai Chen ◽  
Lin Guo ◽  
Lei Zhang ◽  
Haoyu Wu ◽  
Jiaqi Yang ◽  
...  
Keyword(s):  
Vitamin C ◽  
Somatic Cell ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming

scholarly journals Coordination of Engineered Factors with TET1/2 Promotes Early-Stage Epigenetic Modification during Somatic Cell Reprogramming

2014 ◽  
Vol 2 (3) ◽  
pp. 253-261 ◽  
Author(s):  
Gengzhen Zhu ◽  
Yujing Li ◽  
Fei Zhu ◽  
Tao Wang ◽  
Wensong Jin ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Early Stage ◽  
Epigenetic Modification ◽  
Cell Reprogramming ◽  
Somatic Cell Reprogramming

scholarly journals Panobinostat Effectively Increases Histone Acetylation and Alters Chromatin Accessibility Landscape in Canine Embryonic Fibroblasts but Does Not Enhance Cellular Reprogramming

2021 ◽  
Vol 8 ◽  
Author(s):  
Maryam Moshref ◽  
Maria Questa ◽  
Veronica Lopez-Cervantes ◽  
Thomas K. Sears ◽  
Rachel L. Greathouse ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Histone Acetylation ◽  
Chromatin Condensation ◽  
Combined Treatment ◽  
Chromatin Accessibility ◽  
Cellular Reprogramming ◽  
Cell Reprogramming ◽  
Embryonic Fibroblasts ◽  
Somatic Cell Reprogramming ◽  
Reprogramming Efficiency

Robust and reproducible protocols to efficiently reprogram adult canine cells to induced pluripotent stem cells are still elusive. Somatic cell reprogramming requires global chromatin remodeling that is finely orchestrated spatially and temporally. Histone acetylation and deacetylation are key regulators of chromatin condensation, mediated by histone acetyltransferases and histone deacetylases (HDACs), respectively. HDAC inhibitors have been used to increase histone acetylation, chromatin accessibility, and somatic cell reprogramming in human and mice cells. We hypothesized that inhibition of HDACs in canine fibroblasts would increase their reprogramming efficiency by altering the epigenomic landscape and enabling greater chromatin accessibility. We report that a combined treatment of panobinostat (LBH589) and vitamin C effectively inhibits HDAC function and increases histone acetylation in canine embryonic fibroblasts in vitro, with no significant cytotoxic effects. We further determined the effect of this treatment on global chromatin accessibility via Assay for Transposase-Accessible Chromatin using sequencing. Finally, the treatment did not induce any significant increase in cellular reprogramming efficiency. Although our data demonstrate that the unique epigenetic landscape of canine cells does not make them amenable to cellular reprogramming through the proposed treatment, it provides a rationale for a targeted, canine-specific, reprogramming approach by enhancing the expression of transcription factors such as CEBP.

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