Reprogramming the Epigenome With Vitamin C

被引:80
|
作者
Chong, Taylor Lee [1 ]
Ahearn, Emily L. [1 ]
Cimmino, Luisa [1 ,2 ]
机构
[1] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA
[2] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
关键词
vitamin C; stem cell reprogramming; TET; Jumonji C; cancer; PLURIPOTENT STEM-CELLS; HYPOXIA-INDUCIBLE FACTORS; ACUTE MYELOID-LEUKEMIA; ASCORBIC-ACID; DNA METHYLATION; GENE-EXPRESSION; HISTONE DEMETHYLASES; COLLAGEN-SYNTHESIS; TET PROTEINS; PHARMACOLOGICAL ASCORBATE;
D O I
10.3389/fcell.2019.00128
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The erasure of epigenetic modifications across the genome of somatic cells is an essential requirement during their reprogramming into induced pluripotent stem cells (iPSCs). Vitamin C plays a pivotal role in remodeling the epigenome by enhancing the activity of Jumonji-C domain-containing histone demethylases (JHDMs) and the ten-eleven translocation (TET) proteins. By maintaining differentiation plasticity in culture, vitamin C also improves the quality of tissue specific stem cells derived from iPSCs that are highly sought after for use in regenerative medicine. The ability of vitamin C to potentiate the activity of histone and DNA demethylating enzymes also has clinical application in the treatment of cancer. Vitamin C deficiency has been widely reported in cancer patients and has recently been shown to accelerate cancer progression in disease models. Therapies involving high-dose vitamin C administration are currently gaining traction in the treatment of epigenetic dysregulation, by targeting aberrant histone and DNA methylation patterns associated with cancer progression.
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页数:13
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