Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states

摘要: The inner cell mass of the mouse pre-implantation blastocyst comprises epiblast progenitor and primitive endoderm cells which cognate embryonic (mESCs) or extra-embryonic (XEN) stem lines can be derived. Importantly, each type retains defining properties lineage restriction their in vivo tissue origin. Recently, we demonstrated that XEN-like arise within mESC cultures. This raises possibility mESCs generate self-renewing XEN without requirement for gene manipulation. We have developed a novel approach to convert (cXEN) using growth factors. confirm downregulation pluripotency transcription factor Nanog expression endoderm-associated genes Gata6, Gata4, Sox17 Pdgfra are necessary cXEN derivation. highlights an important function Fgf4 Paracrine FGF signalling compensates loss endogenous Fgf4, is exit self-renewal, but not maintenance. Our protocol also reveals distinct pluripotent respond uniquely differentiation promoting signals. derived from cultured with Erk Gsk3 inhibitors (2i), LIF, similar conventional mESCs. However, find (EpiSCs) post-implantation embryo refractory establishment, consistent hypothesis EpiSCs represent state In all, these findings suggest potential includes capacity give rise both lineages.