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Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage

View ORCID ProfileQifan Zhu, Fei Sang, Sarah Withey, Walfred Tang, Sabine Dietmann, View ORCID ProfileDoris Klisch, View ORCID ProfilePriscila Ramos-Ibeas, View ORCID ProfileHaixin Zhang, View ORCID ProfileCristina E. Requena, View ORCID ProfilePetra Hajkova, View ORCID ProfileMatt Loose, View ORCID ProfileM. Azim Surani, View ORCID ProfileRamiro Alberio
doi: https://doi.org/10.1101/2020.08.07.241075
Qifan Zhu
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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Fei Sang
2School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
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Sarah Withey
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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Walfred Tang
3Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
4Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
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Sabine Dietmann
3Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
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Doris Klisch
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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Priscila Ramos-Ibeas
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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Haixin Zhang
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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Cristina E. Requena
5MRC London Institute of Medical Sciences (LMS), London, UK
6Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK
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Petra Hajkova
5MRC London Institute of Medical Sciences (LMS), London, UK
6Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK
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Matt Loose
2School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
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M. Azim Surani
3Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
4Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
7Wellcome Trust Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
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  • For correspondence: Ramiro.alberio@nottingham.ac.uk Azim.surani@gurdon.cam.ac.uk
Ramiro Alberio
1School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK
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  • For correspondence: Ramiro.alberio@nottingham.ac.uk Azim.surani@gurdon.cam.ac.uk
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Summary

Investigations on the human germline and programming are challenging due to limited access to embryonic material. However, the pig as a model may provide insight on transcriptional network and epigenetic reprogramming applicable to both species. Here we show that during the pre- and early migratory stages pig primordial germ cells (PGCs) initiate large-scale epigenetic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and potentially base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3, as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, including in vitro gametogenesis.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 07, 2020.
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Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage
Qifan Zhu, Fei Sang, Sarah Withey, Walfred Tang, Sabine Dietmann, Doris Klisch, Priscila Ramos-Ibeas, Haixin Zhang, Cristina E. Requena, Petra Hajkova, Matt Loose, M. Azim Surani, Ramiro Alberio
bioRxiv 2020.08.07.241075; doi: https://doi.org/10.1101/2020.08.07.241075
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Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage
Qifan Zhu, Fei Sang, Sarah Withey, Walfred Tang, Sabine Dietmann, Doris Klisch, Priscila Ramos-Ibeas, Haixin Zhang, Cristina E. Requena, Petra Hajkova, Matt Loose, M. Azim Surani, Ramiro Alberio
bioRxiv 2020.08.07.241075; doi: https://doi.org/10.1101/2020.08.07.241075

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