PT - JOURNAL ARTICLE AU - Shlomit Edri AU - Penny Hayward AU - Peter Baillie-Johnson AU - Benjamin Steventon AU - Alfonso Martinez Arias TI - An Epiblast Stem Cell derived multipotent progenitor population for axial extension AID - 10.1101/242461 DP - 2018 Jan 01 TA - bioRxiv PG - 242461 4099 - http://biorxiv.org/content/early/2018/05/18/242461.short 4100 - http://biorxiv.org/content/early/2018/05/18/242461.full AB - The Caudal Lateral Epiblast of mammalian embryos harbours bipotent progenitors that contribute to the spinal cord and the paraxial mesoderm in concert with the elongation of the body axis. 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, additional to NMPs, generates 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 self renew in vitro and exhibit a gene expression signature similar to that of their embryo counterparts.