The critical role of the placenta in supporting a healthy pregnancy is mostly ensured by the extraembryonic trophoblast lineage that acts as the interface between the maternal and the foetal compartments. The diverse trophoblast cell subtypes that form the placenta originate from a single layer of stem cells that emerge from the embryo when the earliest cell fate decisions are occurring. Recent studies show that these trophoblast stem cells exhibit extensive plasticity as they are capable of differentiating down multiple pathways and are easily converted into embryonic stem cells in vitro. In this review, we discuss current knowledge of the mechanisms and control of the epigenesis of mouse trophoblast stem cells through a comparison with the corresponding mechanisms in pluripotent embryonic stem cells. To illustrate some of the more striking manifestations of the epigenetic plasticity of mouse trophoblast stem cells, we discuss them within the context of two paradigms of epigenetic regulation of gene expression: the imprinted gene expression of specific loci and the process of X-chromosome inactivation.

BackgroundIn female mice, while the presence of two-active X-chromosomes characterises pluripotency, it is not tolerated in most other cellular contexts. In particular, in the trophoblastic lineage, impairment of paternal X (XP) inactivation results in placental defects.ResultsHere, we show that Trophoblast Stem (TS) cells can undergo a complete reversal of imprinted X-inactivation without detectable change in cell-type identity. This reversal occurs through a reactivation of the XP leading to TS clones showing two active Xs. Intriguingly, within such clones, all the cells rapidly and homogeneously either re-inactivate the XP or inactivate, de novo, the XM.ConclusionThis secondary non-random inactivation suggests that the two-active-X states in TS and in pluripotent contexts are epigenetically distinct. These observations also reveal a pronounced plasticity of the TS epigenome allowing TS cells to dramatically and accurately reprogram gene expression profiles. This plasticity may serve as a back-up system when X-linked mono-allelic gene expression is perturbed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-015-0044-2) contains supplementary material, which is available to authorised users.

Les avancées techniques en biologie de synthèse rendent de plus en plus accessibles la modification ou même la fabrication de virus en laboratoire. Plusieurs travaux de recherche fondés sur la synthèse de pathogènes à potentiel pandémique ont créé la polémique au cours des années 2010 et, aujourd’hui encore, l’éventualité qu’une fuite de laboratoire soit à l’origine de la pandémie de Covid-19 fait débat. En France, un vide juridique subsiste concernant la synthèse de pathogènes modifiés. Une réflexion concertée vers un encadrement légal de ce type de recherche apparaît donc nécessaire et urgent pour que la recherche continue de représenter un bénéfice, plutôt qu’un risque, pour la société.