Neuro-mesodermal progenitors (NMPs): a comparative study between pluripotent stem cells and embryo-derived populations

Abstract

The mammalian embryo's caudal lateral epiblast (CLE) harbours bipotent progenitors, called neural mesodermal progenitors (NMPs), that contribute to the spinal cord and the paraxial mesoderm throughout axial elongation. Here, we performed a single cell analysis of different <i>in vitro</i> NMP populations produced either from embryonic stem cells (ESCs) or epiblast stem cells (EpiSCs) and compared them with E8.25 CLE mouse embryos. In our analysis of this region, our findings challenge the notion that NMPs can be defined by the exclusive co-expression of <i>Sox2</i> and <i>T</i> at mRNA level. We analyse the <i>in vitro</i> NMP-like populations using a purpose-built support vector machine (SVM) based on the embryo CLE and use it as a classification model to compare the <i>in vivo</i> and <i>in vitro</i> populations. Our results show that NMP differentiation from ESCs leads to heterogeneous progenitor populations with few NMP-like cells, as defined by the SVM algorithm, whereas starting with EpiSCs yields a high proportion of cells with the embryo NMP signature. We find that the population from which the Epi-NMPs are derived in culture contains a node-like population, which suggests that this population probably maintains the expression of <i>T in vitro</i> and thereby a source of NMPs. In conclusion, differentiation of EpiSCs into NMPs reproduces events <i>in vivo</i> and suggests a sequence of events for the emergence of the NMP population.