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

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 epigen...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255163/
https://www.ncbi.nlm.nih.gov/pubmed/30381455
http://dx.doi.org/10.1073/pnas.1814514115
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author 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
author_facet 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
author_sort Yu, Dawei
collection PubMed
description 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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spelling pubmed-62551632018-11-30 Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning 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 Proc Natl Acad Sci U S A PNAS Plus 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. National Academy of Sciences 2018-11-20 2018-10-31 /pmc/articles/PMC6255163/ /pubmed/30381455 http://dx.doi.org/10.1073/pnas.1814514115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
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
Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title_full Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title_fullStr Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title_full_unstemmed Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title_short Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
title_sort silencing of retrotransposon-derived imprinted gene rtl1 is the main cause for postimplantational failures in mammalian cloning
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255163/
https://www.ncbi.nlm.nih.gov/pubmed/30381455
http://dx.doi.org/10.1073/pnas.1814514115
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