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Comparison of DNA methylation between two types of mouse pluripotent stem cells: ESCs and EpiSCs

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Veillard, Anne-Clémence | Bernado, Andreia | Brochard, Vincent | Jouneau, Luc | Pedersen, Roger | Marks, Hendrik | Stunnenberg, Henk | Jouneau, Alice

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Alice Jouneau: Member of the REVIVE LABEX: Stem cells in Regenerative Biology and Medecine
Alice Jouneau: Member of the REVIVE LABEX: Stem cells in Regenerative Biology and Medecine. In mouse, embryonic stem cells (ESCs) are derived from the inner cell mass of the blastocyst and epiblast stem cells (EpiSCs) from the epiblast of post-implantation embryos. Although sharing common pluripotent properties, they have distinct characteristics: ESCs correspond to a naïve state of pluripotency, whereas EpiSCs expressing several markers of gastrulation represent a primed state. How their epigenome differences underpin the phenotypic and molecular characteristics of each state of pluripotency has not yet been well studied. We have compared the methylation patterns in the two epiblast-derived stem cells. Indeed, genome-wide analysis of DNA methylation has revealed important differences, especially on promoters. Some of them have been further validated using cloning sequencing following bisulfite treatment of DNA. Owing to the possibility to inter-convert in vitro the pluripotent cells, we have shown that while methylation is well apposed during conversion from ESCs to EpiSCs, it was not faithfully reprogrammed during reversion of EpiSCs to ESCs. Moreover, our ongoing analysis using ESCs mutant for Dnmts indicates that DNA methylation is mandatory for the formation and/or maintenance of the EpiSC state.

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