Abstract
Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.
Highlights
Pluripotent stem cells are characterized by their ability to expand indefinitely in vitro while retaining the capacity to generate derivatives of all three germ layers, both in vitro and in vivo
ES cells and epiblast stem cells (EpiSCs) are both pluripotent as they are capable of generating derivatives of the three embryonic germ layers upon in vitro or in vivo differentiation, yet important molecular and functional differences exist between these two pluripotent states
The ES cell pluripotent state is maintained by a combination of LIF/JAK/STAT3 and BMP4 signaling, while EpiSCs require a combination of bFGF and TGFb/Activin signaling for their continued self-renewal
Summary
Pluripotent stem cells are characterized by their ability to expand indefinitely in vitro while retaining the capacity to generate derivatives of all three germ layers, both in vitro and in vivo. ES cells and EpiSCs are both pluripotent as they are capable of generating derivatives of the three embryonic germ layers upon in vitro or in vivo differentiation, yet important molecular and functional differences exist between these two pluripotent states. The different culture conditions that maintain ES cells and EpiSCs are reflected in the morphological, molecular and functional properties of these cells. Murine ES cells form dome-shaped three dimensional colonies and are capable of generating chimeras with functional contribution to all somatic lineages as well as the germline. EpiSCs are pluripotent and form derivatives of all three germ layers during in vitro differentiation and upon teratoma formation in vivo. While EpiSCs are pluripotent, to-date their in vivo developmental potential is limited to teratoma formation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
