BMS Seminar at CSRL: Identification of the Anterior Hypoblast Signalling Centre in Human Embryos, Dr Matteo Molè, Postdoctoral Research Associate, University of Cambridge and Clare College Cambridge
Abstract: Upon implantation, the human embryo undergoes major morphogenetic transformations that are fundamental for the establishment of the future body plan. A key step for the formation the anterior-posterior body axis is a symmetry breaking event within the embryonic epiblast. While the molecular events that underpin this symmetry breaking step in mice are well established, they remain unknown in human embryos. By applying single-cell mRNA sequencing to embryos cultured ex vivo, we have identified the sequence of events that underlies epiblast development and symmetry breaking prior to gastrulation. We determined the epiblast as a major source of FGF signals, which are essential for the maintenance of epiblast and hypoblast during early post-implantation development. We found that epiblast cells transition through different pluripotent states before being exposed to the inhibitory action of WNT, BMP and NODAL antagonists in a polarised manner. These inhibitors are secreted by a subset of asymmetrically distributed hypoblast cells, which form a local signalling centre, the anterior hypoblast, reminiscent of the anterior visceral endoderm of the pre-gastrulation mouse embryo. Our study provides the first insights into the mechanism that leads to the establishment of the anterior-posterior axis in the human embryo.