Lee Chong Taylor, Ahearn Emily L, Cimmino Luisa
Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, United States.
Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, United States.
Front Cell Dev Biol. 2019 Jul 16;7:128. doi: 10.3389/fcell.2019.00128. eCollection 2019.
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.
在体细胞重编程为诱导多能干细胞(iPSC)的过程中,擦除全基因组的表观遗传修饰是一项基本要求。维生素C通过增强含Jumonji-C结构域的组蛋白去甲基化酶(JHDM)和10-11易位(TET)蛋白的活性,在重塑表观基因组中发挥关键作用。通过在培养中维持分化可塑性,维生素C还提高了源自iPSC的组织特异性干细胞的质量,这些干细胞在再生医学中备受青睐。维生素C增强组蛋白和DNA去甲基化酶活性的能力在癌症治疗中也有临床应用。癌症患者中维生素C缺乏的情况已被广泛报道,最近还显示在疾病模型中维生素C缺乏会加速癌症进展。目前,通过针对与癌症进展相关的异常组蛋白和DNA甲基化模式,涉及大剂量维生素C给药的疗法在治疗表观遗传失调方面正越来越受到关注。