MeCP2 deficiency promotes cell reprogramming by stimulating IGF1/AKT/mTOR signaling and activating ribosomal protein-mediated cell cycle gene translation

MeCP2 缺乏通过刺激 IGF1/AKT/mTOR 信号传导和激活核糖体蛋白介导的细胞周期基因翻译来促进细胞重编程

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作者:Wei Zhang, Guihai Feng, Libin Wang, Fei Teng, Liu Wang, Wei Li, Ying Zhang, Qi Zhou

Abstract

The generation of induced pluripotent stem cells (iPSCs) offers a great opportunity in research and regenerative medicine. The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hamper the clinical application of iPSCs. MeCP2 connects histone modification and DNA methylation, which are key changes of somatic cell reprogramming. However, the role of MeCP2 in cell reprogramming has not been examined. In this study, we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the early stage of reprogramming. MeCP2 deficiency enhanced the expression of ribosomal protein genes, thereby enhancing reprogramming efficiency through promoting the translation of cell cycle genes. In the end, MeCP2 deficiency stimulated IGF1/AKT/mTOR signaling and activated ribosomal protein gene expression. Taken together, our data indicate that MeCP2 deficiency promoted cell reprogramming through stimulating IGF1/AKT/mTOR signaling and activating ribosomal protein-mediated cell cycle gene translation in the early stage of reprogramming.

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