Proceedings of the National Academy of Sciences of the United States of America · 2018
Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yu Dawei, Wang Jing, Zou Huiying, Feng Tao, Chen Lei, Li Jia, Qi Xiaolan, Li Zhifang, Duan Xiaoyue, Xu Chunlong, Zhang Liang, Long Xi, Lan Jing, Chen Chao, Wang Chao, Xu Xinyu, Ren Jilong, Zhao Yiqiang, Hu Xiaoxiang, Lian Zhengxing, Men Hongsheng, Pan Dengke, Li Ning, Capecchi Mario R, Du Xuguang, Zhao Yaofeng, Wu Sen
Аннотация
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.