Preface
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.
Glossary
- Primordial 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 cells
- in 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 transfer
- cloning 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 pluripotency
- pluripotent state that resembles pre-implantation pluripotent configuration(s).
- Primed pluripotency
- pluripotent state that resembles to post-implantation embryonic configuration(s).
- Ground state pluripotency
- originally described as a state of pluripotency that is independent of exogenous activator signalling input or stimulation.
- X inactivation
- dosage compensation of X chromosome in female, where one of the X chromosomes gets epigenetically silenced.
- Seed enhancers
- subgroup of enhancers that are dormant in naive cells but become more active in primed pluripotent and somatic cells.
- 3i
- Defined naïve pluripotency growth conditions combing 3 inhibitors (i) for MEK, FGF and GSK3 signalling.
- 2i/LIF
- Defined 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 pathways
- LIF/MEKi/aPKCi
- Defined naïve pluripotency growth conditions containing 2 inhibitors (i) for MEK and atypical PKC signalling, together with LIF cytokine.
- FGF2/ACTIVIN A
- Defined primed pluripotency growth conditions for mouse EpiSCs composed of recombinant FGF2 and ACTIVIN A cytokines.
- GSK3i/IWR1
- Defined primed pluripotency growth conditions for mouse EpiSCs composed of GSK3 pathway inhibitor and Tankyrase small molecule inhibitor, IWR1.
- FGF2/IWR1
- Defined primed pluripotency growth conditions for mouse EpiSCs composed of recombinant FGF2 and Tankyrase small molecule inhibitor, IWR1.