The emergent landscape of the mouse gut endoderm at single-cell resolution

To delineate the ontogeny of the mammalian endoderm, we generated 112,217 single-cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. By employing graph-based approaches, we modelled differentiating cells for spatio-temporal characterization of developmental trajectories and defined the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncovered a relationship between descendants of these two lineages, whereby epiblast cells differentiate into endoderm at two distinct time-points, before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates, and as they spatially converged within the nascent gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observed the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, reflecting their embryonic or extra-embryonic origin, and their coordinate patterning into organ-specific territories.