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A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.

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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.



Bone Morphogenetic Protein 1, Cell Lineage, Cells, Cultured, Embryo Implantation, Embryo, Mammalian, Embryonic Development, Fibroblast Growth Factors, Gastrulation, Gene Expression Regulation, Developmental, Germ Layers, Humans, Image Processing, Computer-Assisted, Multigene Family, Nodal Protein, RNA-Seq, Single-Cell Analysis, Spatio-Temporal Analysis, Wnt Signaling Pathway

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Nat Commun

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Springer Science and Business Media LLC


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Wellcome Trust (207415/Z/17/Z)
M.N.S is funded by the European Molecular Biology Organisation (EMBO, Advanced EMBO fellowship) and UKRI Medical Research Council (MC_UP_1201/24). B.A.T.W is funded by the Gates Cambridge Trust. Work in the laboratory of M.Z-G. is supported by grants from the Wellcome Trust (207415/Z/17/Z), Open Philanthropy/Silicon Valley, Curci and Weston Havens Foundations. S.B is funded by the Wellcome Trust (Sanger core funding and personal fellowship to S.B.).