Zfp281 is essential for epiblast maturation through a cell autonomous effect.

Pluripotency is recognized as a spectrum of cellular states span-ning the naive pluripotency established in the preimplantation blasto-cyst and its transition into primed pluripotency in the postimplantation epiblast cells.The exit from pluripotency is followed by the initiation of gastrulation(Brennan et al.,2001;Nichols and Smith,2009).Naive to primed pluripotent state transition is essential for cell fate decisions,establishing the correct body plan during mammalian embryo development.Zfp281 is a transcription factor known for its critical role in regulating embryonic stem cell(ESC)plu-ripotency by promoting the naive to primed pluripotent state transi-tion from our in vitro studies of ESCs and epiblast stem cells(EpiSCs)(Fidalgo etal.,2011,2012;Huang et al.,2017).Our previous work using a global null allele to generate the conventional knockout mouse model also confirmed a key role ofZfp281 in the epiblast line-age of the developing embryo,manifested by embryonic lethality due to a failure in epiblast maturation(Huang et al.,2017).Zfp281 is expressed in the pluripotent epiblast and its derivatives and directs the activation of target genes in lineage specification and embryo development.Mechanistically,Zfp281 cooperates with epigenetic regulators at targeted gene promotors and enhancers to transcrip-tionally regulate the expression of Nodal signaling pathway genes.Zfp281 global loss leads to defects in the anterior-posterior(A-P)specification during epiblast maturation(Huang et al.,2017).