Specification and epigenomic 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
Affiliations
Qifan Zhu
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
Fei Sang
School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK
Sarah Withey
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
Walfred Tang
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
Sabine Dietmann
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Doris Klisch
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
Priscila Ramos-Ibeas
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
Haixin Zhang
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
Cristina E. Requena
MRC London Institute of Medical Sciences (LMS), London, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK
Petra Hajkova
MRC London Institute of Medical Sciences (LMS), London, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK
Matt Loose
School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK
M. Azim Surani
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; Wellcome Trust Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Corresponding author
Ramiro Alberio
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK; Corresponding author
Summary: Investigations of the human germline and programming are challenging because of limited access to embryonic material. However, the pig as a model may provide insights into 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 epigenomic 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.
