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Dynamic of nuclear changes occurring during the conversion between naïve (ESCs) and primed (EpiSCs) pluripotent cells

Abstract : Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent naïve and primed pluripotency states, respectively and are maintained in vitro using specific signaling pathways. Furthermore, ESCs cultured in serum-free medium with two inhibitors (2i) are described as being the most naïve. Several studies have suggested that each pluripotent cell type is characterized by a different epigenome organization. Here we present a comparative study of the epigenetic and transcriptional state of centromeric and pericentromeric (CH/PCH) satellite repeats in ESCs (2i and serum ones) and EpiSCs. We show that the pattern of H3K27me3 at PCH is highly dynamic and discriminate 2i-ESCs from the other pluripotent stem cells. Whereas satellites transcription is high in serum-ESCs, it is lower in 2i-ESCs and even more repressed in EpiSCs. Removal of either DNA methylation or H3K9me3 in ESCs leads to enhanced deposition of H3K27me3 but few changes in satellite transcription. By contrast, in EpiSCs removal of H3K9me3 does not prevent DNA methylation at PCH but de-represses the satellite transcription. In vitro conversion from naive to primed pluripotency showed an important delay compared to the in vivo development of ICM cells into post-implantation epiblast. Such inefficiency cannot be explained by a delayed switch to the new transcriptional network. Altogether our study reveals that EpiSCs have lost the chromatin plasticity of ESCs on heterochromatin as well as euchromatin, as shown by the reduction of H3K9ac levels and bivalent domains, thus being closer to somatic cells in terms of epigenetics than naive pluripotency.
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https://theses.hal.science/tel-01552175
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Submitted on : Saturday, July 1, 2017 - 1:03:46 AM
Last modification on : Thursday, April 21, 2022 - 3:57:54 PM
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  • HAL Id : tel-01552175, version 1
  • PRODINRA : 382676

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Matteo Tosolini. Dynamic of nuclear changes occurring during the conversion between naïve (ESCs) and primed (EpiSCs) pluripotent cells. Subcellular Processes [q-bio.SC]. Université Paris Saclay (COmUE), 2016. English. ⟨NNT : 2016SACLS511⟩. ⟨tel-01552175⟩

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