|Dawei Yu, Jing Wang, Huiying Zou, Tao Feng, Lei Chen, Zhifang Li, Xiaoyue Duan, Yaofeng Zhao and Sen Wu. Silencing of retrotransposon-derived imprinted geneRTL1 is the main cause for postimplantationalfailures in mammalian cloning. PNAS. DOI: 10.1073/pnas|
Silencing of retrotransposon-derived imprinted geneRTL1 is the main cause for postimplantationalfailures in mammalian cloning
Dawei Yu, Jing Wang, Huiying Zou, Tao Feng, Lei Chen, Jia Li, Xiaolan Qi, Zhifang Li, Xiaoyue Duan, Chunlong Xu, Liang Zhang, Xi Long, Jing Lan, Chao Chen, Chao Wang, Xinyu Xu, Jilong Ren, Yiqiang Zhao, Xiaoxiang Hu, Zhengxing Lian, Hongsheng Men, Dengke Pan, Ning Li, Mario R. Capecchi, Xuguang Du, Yaofeng Zhao and Sen Wu
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 aretypically 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, lowRTL1 levels appear to be the main epigenetic cause of pregnancy failure.