Abstract
SummaryInvestigations 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.
Highlights
The germline transmits hereditary information, which ensures continuity of the species
Studies of early human PGCs (hPGCs) have relied on pluripotent stem cellbased in vitro models, which showed that hPGC-like cells (hPGCLCs) originate from cells with a posterior primitive streak (PS)/incipient mesoderm-like identity following exposure to BMP, revealing SOX17 to be a critical determinant of the primordial germ cells (PGCs) fate (Irie et al, 2015; Kojima et al, 2017)
SOX17 protein was present in pre-migratory and gonadal pig PGCs (pPGCs), as observed by immunofluorescence (IF) (Figure 1A; Figure S1A), the SOX17 transcript was found in a subset of pPGCs (6 of 17 in E14 and 12 of 22 in E31 pPGCs) (Figure 1B)
Summary
Zhu et al show that pig primordial germ cells (PGCs) undergo DNA demethylation, histone remodeling, and X chromosome reactivation after specification. Pig PGCs retain few methylated loci after genomewide demethylation, with potential for transgenerational inheritance. Species comparisons shows close similarities in transcriptional profiles of pig and human PGCs. Highlights d Gene expression profiles of pig and human primordial germ cells are closely aligned d Pre-migratory pig PGCs undergo DNA demethylation, XCR, and histone remodeling d Identification of DNA demethylation-resistant loci in the pig germline. February 9, 2021 a 2021 The Authors.
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