TY - JOUR
T1 - Stable methylation at promoters distinguishes epiblast stem cells from embryonic stem cells and the in vivo epiblasts
AU - Veillard, Anne Clémence
AU - Marks, Hendrik
AU - Bernardo, Andreia Sofia
AU - Jouneau, Luc
AU - Laloë, Denis
AU - Boulanger, Laurent
AU - Kaan, Anita
AU - Brochard, Vincent
AU - Tosolini, Matteo
AU - Pedersen, Roger
AU - Stunnenberg, Henk
AU - Jouneau, Alice
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Embryonic Stem Cells (ESCs) and Epiblast Stem Cells (EpiSCs) are the in vitro representatives of naïve and primed pluripotency, respectively. It is currently unclear how their epigenomes underpin the phenotypic and molecular characteristics of these distinct pluripotent states. Here, we performed a genome-wide comparison of DNA methylation between ESCs and EpiSCs by MethylCap-Seq. We observe that promoters are preferential targets for methylation in EpiSC compared to ESCs, in particular high CpG island promoters. This is in line with upregulation of the de novo methyltransferases Dnmt3a1 and Dnmt3b in EpiSC, and downregulation of the demethylases Tet1 and Tet2. Remarkably, the observed DNA methylation signature is specific to EpiSCs and differs from that of their in vivo counterpart, the postimplantation epiblast. Using a subset of promoters that are differentially methylated, we show that DNA methylation is established within a few days during in vitro outgrowth of the epiblast, and also occurs when ESCs are converted to EpiSCs in vitro. Once established, this methylation is stable, as ES-like cells obtained by in vitro reversion of EpiSCs display an epigenetic memory that only extensive passaging and sub-cloning are able to almost completely erase.
AB - Embryonic Stem Cells (ESCs) and Epiblast Stem Cells (EpiSCs) are the in vitro representatives of naïve and primed pluripotency, respectively. It is currently unclear how their epigenomes underpin the phenotypic and molecular characteristics of these distinct pluripotent states. Here, we performed a genome-wide comparison of DNA methylation between ESCs and EpiSCs by MethylCap-Seq. We observe that promoters are preferential targets for methylation in EpiSC compared to ESCs, in particular high CpG island promoters. This is in line with upregulation of the de novo methyltransferases Dnmt3a1 and Dnmt3b in EpiSC, and downregulation of the demethylases Tet1 and Tet2. Remarkably, the observed DNA methylation signature is specific to EpiSCs and differs from that of their in vivo counterpart, the postimplantation epiblast. Using a subset of promoters that are differentially methylated, we show that DNA methylation is established within a few days during in vitro outgrowth of the epiblast, and also occurs when ESCs are converted to EpiSCs in vitro. Once established, this methylation is stable, as ES-like cells obtained by in vitro reversion of EpiSCs display an epigenetic memory that only extensive passaging and sub-cloning are able to almost completely erase.
UR - http://www.scopus.com/inward/record.url?scp=84906545071&partnerID=8YFLogxK
U2 - 10.1089/scd.2013.0639
DO - 10.1089/scd.2013.0639
M3 - Article
C2 - 24738887
AN - SCOPUS:84906545071
SN - 1547-3287
VL - 23
SP - 2014
EP - 2029
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 17
ER -