TY - JOUR T1 - Dynamic stem cell states: naïve to primed pluripotency in rodents and humans JF - bioRxiv DO - 10.1101/030676 SP - 030676 AU - Leehee Weinberger AU - Muneef Ayyash AU - Noa Novershtern AU - Jacob H. Hanna Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/12/12/030676.abstract N2 - The molecular mechanisms and signalling pathways that regulate the in vitro preservation of distinct pluripotent stem cell configurations, and their induction in somatic cells via direct reprogramming approaches, continue to constitute a highly exciting area of research. In this review, we provide an integrative synthesis on recent discoveries related to isolating unique naïve and primed pluripotent stem cell states with altered functional and molecular characteristics, and from different species. We overview pathways underlying pluripotent state transitions and interconversion in vitro and in vivo. We conclude by highlighting unresolved key questions, future directions and potential novel applications of such dynamic pluripotent cell states.GlossaryPrimordial germ cells (PGCs)embryonic progenitor cells that give rise to germ cells in the gonads (sperm and oocytes).Inner cell mass (ICM)the mass of cells inside the pre-implantation blastocyst that will subsequently give rise to the definitive structures of the fetus.Embryonic stem cells (ESCs)in vitro expanded pluripotent cells that originate from the ICM.Epiblast stem cells (EpiSCs)in vitro expanded pluripotent cells that originate from the postimplantation epiblast.Embryonic germ cellsin vitro expanded pluripotent cells that are derived from embryonic PGCs.Germ stem cells (GSCs)in vitro expanded pluripotent stem cells that originate from neonatal or adult testis derived spermatogonial stem cells.Nuclear transfercloning of somatic cell derived nucleus and its introduction into a-nucleated host oocyte.Induced pluripotent stem cells (iPSCs)in vitro generated pluripotent cells derived via ectopic expression of defined exogenous factors in somatic cells.Naïve pluripotencypluripotent state that resembles pre-implantation pluripotent configuration(s).Primed pluripotencypluripotent state that resembles to post-implantation embryonic configuration(s).Ground state pluripotencyoriginally described as a state of pluripotency that is independent of exogenous activator signalling input or stimulation.X inactivationdosage compensation of X chromosome in female, where one of the X chromosomes gets epigenetically silenced.Seed enhancerssubgroup of enhancers that are dormant in naive cells but become more active in primed pluripotent and somatic cells.3iDefined naïve pluripotency growth conditions combing 3 inhibitors (i) for MEK, FGF and GSK3 signalling.2i/LIFDefined naïve pluripotency growth conditions containing 2 inhibitors (i) for MEK and GSK3 together with LIF cytokine.“Alternative 2i”Defined naïve pluripotency growth conditions composed of 2 small molecule inhibitors for GSK3 and SRC pathwaysLIF/MEKi/aPKCiDefined naïve pluripotency growth conditions containing 2 inhibitors (i) for MEK and atypical PKC signalling, together with LIF cytokine.FGF2/ACTIVIN ADefined primed pluripotency growth conditions for mouse EpiSCs composed of recombinant FGF2 and ACTIVIN A cytokines.GSK3i/IWR1Defined primed pluripotency growth conditions for mouse EpiSCs composed of GSK3 pathway inhibitor and Tankyrase small molecule inhibitor, IWR1.FGF2/IWR1Defined primed pluripotency growth conditions for mouse EpiSCs composed of recombinant FGF2 and Tankyrase small molecule inhibitor, IWR1. ER -