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The Abilities of ShDNMT1 to Promote Reprogramming are Enhanced by Vitamin C-recused Proliferation |
LI Ling-yu1,2, HE Song-wei2, ZHENG Hui2 |
1. School of Life Science, Anhui University, Hefei 230601, China;
2. Guangzhou Institute of Biomedicine and Health, CAS, Guangzhou 510530, China |
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Abstract DNA methylation and Vitamin C (Vc) play critical roles during the generation of induced pluripotent stem cells (iPSCs). In current study, the interaction between DNMT1 and Vc during reprogramming process was studied. In the absence of Vc, reducing DNMT1 expression with shRNA did not promote the transition from fibroblasts or pre-iPSC to iPSCs obviously. While when Vc was added in the medium, shDNMT1 increased the generation of iPSCs from both kinds of cells. In addition, shDNMT1 actually inhibited cell proliferation and increased the percentage of cells in G1 phase, which reduced its ability to promote reprogramming partially. Therefore, by promoting cell proliferation, decreasing the percentage of cells in G1 phase, and rescuing the inhibitory effect of shDNMT1 on proliferation, Vc further enhanced the ability of shDNMT1 to promote reprogramming.
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Received: 01 December 2015
Published: 16 March 2016
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[1] Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006,126(4):663-676.
[2] Esteban M A, Tao Wang, Baoming Qin, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell,2010, 6:71-79.
[3] Chen J, He Liu, Jing Liu, et al. H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs. Nat Genet,2013,45:34-42.
[4] Hu X, Lei Zhang, Mao S Q, et al. Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition kin somatic cell reprogramming.Cell Stem Cell,14(4): 512-522.
[5] Shinsuke Ito, Li Shen, Qing Dai, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.Science,2011, 333:1300-1303.
[6] Chen J, Lin Guo, Lei Zhang, et al. Vitamin C modulates TET1 function during somatic cell reprogramming. Nat Genet,2013,45:1504-1510.
[7] Wang T, Chen K, Xeng X M,et al. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell,2011,9:575-587.
[8] Yamanaka S, Blau H M. Nuclear reprogramming to a pluripotent state by three approaches. Nature, 2010,465(7299):704-712.
[9] Li E, Bestor T H, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell,1992, 6(69):915-926.
[10] Leonhardt H, Page A W, Weier H U, et al. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell,1992, 71:865-873.
[11] Voo S, Skalnik D G. Identification and characterization of the DNA binding domain of CpG-binding protein. J Biol Chem,2011,276:44669-44676.
[12] Pauklin1 S, Vallie L.The cell-cycle state of stem cells determines cell fate propensity. Cell,2013, 155: 135-147.
[13] Asako Sakaue-Sawano, Miyawaki A. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression.cell,2007,12(033):487-498.
[14] Hanna J,Krishanu S, Bernardo Pando,et al. Direct cell reprogramming is a stochastic process amenable to aceleration.Nature, 2009,462(7273):595-601.
[15] Ruiz S, Athanasia D. A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity.Current Biology,2011,21(1):45-52.
[16] Edel M J, Izpisua J C.The cell cycle and pluripotency: Is there a direct link? Cell Cycle,2010,9(14):1694-2695. |
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