Reprogramming the Epigenome With Vitamin C

被引：88

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

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2019年 / 7卷

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.

引用

页数：13

共 149 条

[1] Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies [J].

Abdel-Wahab, Omar ;

Mullally, Ann ;

Hedvat, Cyrus ;

Garcia-Manero, Guillermo ;

Patel, Jay ;

Wadleigh, Martha ;

Malinge, Sebastien ;

Yao, JinJuan ;

Kilpivaara, Outi ;

Bhat, Rukhmi ;

Huberman, Kety ;

Thomas, Sabrena ;

Dolgalev, Igor ;

Heguy, Adriana ;

Paietta, Elisabeth ;

Le Beau, Michelle M. ;

Beran, Miloslav ;

Tallman, Martin S. ;

Ebert, Benjamin L. ;

Kantarjian, Hagop M. ;

Stone, Richard M. ;

Gilliland, D. Gary ;

Crispino, John D. ;

Levine, Ross L. .

BLOOD, 2009, 114 (01) :144-147

[2] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis [J].

Agathocleous, Michalis ;

Meacham, Corbin E. ;

Burgess, Rebecca J. ;

Piskounova, Elena ;

Zhao, Zhiyu ;

Crane, Genevieve M. ;

Cowin, Brianna L. ;

Bruner, Emily ;

Murphy, Malea M. ;

Chen, Weina ;

Spangrude, Gerald J. ;

Hu, Zeping ;

DeBerardinis, Ralph J. ;

Morrison, Sean J. .

NATURE, 2017, 549 (7673) :476-+

[3] Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters [J].

Agus, DB ;

Gambhir, SS ;

Pardridge, WM ;

Spielholz, C ;

Baselga, J ;

Vera, JC ;

Golde, DW .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (11) :2842-2848

[4] Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia [J].

Akalin, Altuna ;

Garrett-Bakelman, Francine E. ;

Kormaksson, Matthias ;

Busuttil, Jennifer ;

Zhang, Lu ;

Khrebtukova, Irina ;

Milne, Thomas A. ;

Huang, Yongsheng ;

Biswas, Debabrata ;

Hess, Jay L. ;

Allis, C. David ;

Roeder, Robert G. ;

Valk, Peter J. M. ;

Lowenberg, Bob ;

Delwel, Ruud ;

Fernandez, Hugo F. ;

Paietta, Elisabeth ;

Tallman, Martin S. ;

Schroth, Gary P. ;

Mason, Christopher E. ;

Melnick, Ari ;

Figueroa, Maria E. .

PLOS GENETICS, 2012, 8 (06)

[5]

[Anonymous], NAT GENET

[6] SEVERE HYPOVITAMINOSIS-C IN LUNG-CANCER PATIENTS - THE UTILIZATION OF VITAMIN-C IN SURGICAL REPAIR AND LYMPHOCYTE-RELATED HOST-RESISTANCE [J].

ANTHONY, HM ;

SCHORAH, CJ .

BRITISH JOURNAL OF CANCER, 1982, 46 (03) :354-367

[7] The Use of Intravenous Vitamin C as a Supportive Therapy for a Patient with Glioblastoma Multiforme [J].

Baillie, Nicola ;

Carr, Anitra C. ;

Peng, Selene .

ANTIOXIDANTS, 2018, 7 (09)

[8] Senescence impairs successful reprogramming to pluripotent stem cells [J].

Banito, Ana ;

Rashid, Sheikh T. ;

Acosta, Juan Carlos ;

Li, SiDe ;

Pereira, Carlos F. ;

Geti, Imbisaat ;

Pinho, Sandra ;

Silva, Jose C. ;

Azuara, Veronique ;

Walsh, Martin ;

Vallier, Ludovic ;

Gil, Jesus .

GENES & DEVELOPMENT, 2009, 23 (18) :2134-2139

[9]

Bar-Nur O, 2014, NAT METHODS, V11, P1170, DOI [10.1038/NMETH.3142, 10.1038/nmeth.3142]

[10] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells [J].

Blaschke, Kathryn ;

Ebata, Kevin T. ;

Karimi, Mohammad M. ;

Zepeda-Martinez, Jorge A. ;

Goyal, Preeti ;

Mahapatra, Sahasransu ;

Tam, Angela ;

Laird, Diana J. ;

Hirst, Martin ;

Rao, Anjana ;

Lorincz, Matthew C. ;

Ramalho-Santos, Miguel .

NATURE, 2013, 500 (7461) :222-+

← 1 2 3 4 5 6 7 8 9 10 →