Abstract
Following implantation, the human embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are established in mice, they remain unknown in humans. Here we characterise key events of human embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both embryonic and extra-embryonic tissues. In a subset of embryos, we identify a group of asymmetrically positioned extra-embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during human embryo development.
Highlights
Following implantation, the human embryo undergoes major morphogenetic transformations that establish the future body plan
We analysed a total of 29 embryos by single-cell RNA sequencing using 10x Genomics Chromium[26] (Supplementary Data 1). 13 out of 29 embryos lacked inner cell mass (ICM) derivatives, either embryonic epiblast cells or extra-embryonic hypoblast cells, and were excluded from downstream analyses
Despite the reduction in cell number, embryos treated with LY were able to attach and progress in their development. These results suggest that fibroblast growth factor (FGF) signalling is necessary for proliferation of the epiblast, hypoblast and trophoblast lineages, even though we cannot rule out that the reduction of hypoblast cells observed could be due to the reduction of epiblast cells and thereby an indirect effect of FGF inhibition
Summary
The human embryo undergoes major morphogenetic transformations that establish the future body plan. A subset of distal extraembryonic endoderm cells is specified as the distal visceral endoderm (DVE), which migrates towards the future anterior domain giving rise to the anterior visceral endoderm (AVE)[14,15,16,17,18,19] These AVE cells secrete NODAL, BMP and WNT inhibitors, leading to a gradient of signalling activity across the epiblast that defines the AP axis[13]. At 9 d.p.f., a subset of hypoblast cells reminiscent of the anterior visceral endoderm in the pregastrulation mouse embryo emerges These cells secrete conserved inhibitors of the NODAL, BMP and WNT signalling pathways, and could initiate patterning of the anterior-posterior axis prior to gastrulation
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