An Epiblast Stem Cell derived multipotent progenitor population for axial extension

Abstract

The caudal lateral epiblast of mammalian embryos 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 that co-express <i>Sox2</i> and <i>T/</i>brachyury, a criterion used to derive NMP-like cells from embryonic stem cells <i>in vitro</i> However, unlike embryonic NMPs, these progenitors do not self-renew. Here, we find that the protocols that yield NMP-like cells <i>in vitro</i> initially produce a multipotent population that, in addition to NMPs, generates progenitors for the lateral plate and intermediate mesoderm. We show that epiblast stem cells (EpiSCs) are an effective source of these multipotent progenitors, which are further differentiated by a balance between BMP and Nodal signalling. Importantly, we show that NMP-like cells derived from EpiSCs exhibit limited self-renewal <i>in vitro</i> and a gene expression signature like their embryonic counterparts.