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09.02.21 Pig primordial germ cells show epigenetic programme that mimics equivalent human cells in vitro

last modified Feb 11, 2021 09:35 PM
The Surani lab, with collaborators in the Alberio lab at University of Nottingham, show that pig PGCs undergo a transcriptional programme and epigenetic remodelling that closely follows that in the human germline. The pig PGCs could therefore provide a valuable model to validate the findings on human PGCs that are difficult to investigate in our species
09.02.21 Pig primordial germ cells show epigenetic programme that mimics equivalent human cells in vitro

Time course of resetting of chromatin marks in pig PGCs

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

 Zhu Q et al. (2021) Cell Reports 34: 108735.

DOI: 10.1016/j.celrep.2021.108735.

 

 

Highlights from the paper

  • Gene expression profiles of pig and human primordial germ cells are closely aligned
  • Pre-migratory pig PGCs undergo DNA demethylation, XCR, and histone remodeling
  • Identification of DNA demethylation-resistant loci in the pig germline

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.

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The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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