Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning

文献类型： 外文期刊

第一作者： Yu, Dawei

作者： Yu, Dawei;Wang, Jing;Zou, Huiying;Li, Zhifang;Duan, Xiaoyue;Xu, Chunlong;Zhao, Yiqiang;Hu, Xiaoxiang;Li, Ning;Du, Xuguang;Zhao, Yaofeng;Wu, Sen;Yu, Dawei;Ren, Jilong;Zou, Huiying;Pan, Dengke;Feng, Tao;Qi, Xiaolan;Feng, Tao;Qi, Xiaolan;Chen, Lei;Zhang, Liang;Long, Xi;Lan, Jing;Li, Jia;Chen, Chao;Wang, Chao;Xu, Xinyu;Lian, Zhengxing;Du, Xuguang;Men, Hongsheng;Men, Hongsheng;Capecchi, Mario R.

作者机构：

关键词： RTL1; pregnancy failure; DNA methylation; genomic imprinting; nuclear transfer

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.205； 五年影响因子：12.291 ）

ISSN： 0027-8424

年卷期： 2018 年 115 卷 47 期

页码：

收录情况： SCI

摘要： Substantial rates of fetal loss plague all in vitro procedures involving embryo manipulations, including human-assisted reproduction, and are especially problematic for mammalian cloning where over 90% of reconstructed nuclear transfer embryos are typically lost during pregnancy. However, the epigenetic mechanism of these pregnancy failures has not been well described. Here we performed methylome and transcriptome analyses of pig induced pluripotent stem cells and associated cloned embryos, and revealed that aberrant silencing of imprinted genes, in particular the retrotransposon-derived RTL1 gene, is the principal epigenetic cause of pregnancy failure. Remarkably, restoration of RTL1 expression in pig induced pluripotent stem cells rescued fetal loss. Furthermore, in other mammals, including humans, low RTL1 levels appear to be the main epigenetic cause of pregnancy failure.

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