Formative pluripotent stem cells show features of epiblast cells poised for gastrulation

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The pluripotency of mammalian early and late epiblast could be recapitulated by na(i)ve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs),respectively.However,these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development.Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation.fPSCs can be established from different mouse ESCs,pre-/early-gastrula epiblasts and induced PSCs.Similar to pre-/early-gastrula epiblasts,fPSCs show the transcriptomic features of formative pluripotency,which are distinct from na(i)ve ESCs and primed EpiSCs.fPSCs show the unique epigenetic states of E6.5 epiblast,including the super-bivalency of a large set of developmental genes.Just like epiblast cells immediately before gastrulation,fPSCs can efficiently differentiate into three germ layers andprimordial germ cells (PGCs) in vitro.Thus,fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.
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