An Epiblast Stem Cell derived multipotent progenitor population for axial extension.

The mammalian embryos Caudal Lateral Epiblast harbours bipotent progenitors that contribute to the spinal cord and the paraxial mesoderm in concert with the body axis elongation. These progenitors, called Neural Mesodermal Progenitors (NMPs) are identified as cells coexpressing Sox2 and T/Brachyury , a criterion used to derive NMP-like cells from embryonic stem cells in vitro However, these progenitors do not self renew, as embryonic NMPs do. Here we find that protocols that yield NMP-like cells in vitro first produce a multipotent population that, in addition to NMPs, generate progenitors for the lateral plate and intermediate mesoderm. We show that Epiblast Stem Cells (EpiSCs) are an effective source for these multipotent progenitors that are further differentiated by a balance between BMP and Nodal signalling. Importantly, we show that NMP-like cells derived from EpiSCs can be maintained in vitro and exhibit a gene expression signature like their embryonic counterparts.