维生素C对细胞增殖的挽救提高shDNMT1对重编程的促进作用

在利用4个转录因子(Oct4,Sox2,Klf4,c-Myc)获得诱导多能干细胞(iPSC)的过程中,DNA甲基化以及维生素C(Vc)发挥着重要的作用。为了研究DNMT1和维生素C在这一过程中的相互作用,在不使用Vc的情况下,利用shRNA抑制DNMT1 的表达不能有效促进成纤维细胞向iPSC以及pre-iPSC向iPSC的转变。但是,在使用Vc的情况下,shDNMT1可以有效地促进这两种转变。此外,shDNMT1可以抑制成纤维细胞增殖,增大G1期细胞比例。从而在一定程度上抑制shDNMT1对iPSC获得的促进作用。而Vc则可以通过促进细胞增殖,减小G1期细胞比例,挽救 shDNMT1对细胞周期的影响,进而提高shDNMT1对重编程的促进作用。

The Abilities of ShDNMT1 to Promote Reprogramming are Enhanced by Vitamin C-recused Proliferation

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.