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Nat Cell Biol. 2016 Jun;18(6):700-708. doi: 10.1038/ncb3347. Epub 2016 May 4.

Self-organization of the human embryo in the absence of maternal tissues.

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Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
Faculty of Life Sciences and Medicine, King's College London, Women's Health Academic Centre, Assisted Conception Unit, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
Human Embryo and Stem Cell Laboratory, Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK.
CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, NG8 6PZ, UK.
Contributed equally


Remodelling of the human embryo at implantation is indispensable for successful pregnancy. Yet it has remained mysterious because of the experimental hurdles that beset the study of this developmental phase. Here, we establish an in vitro system to culture human embryos through implantation stages in the absence of maternal tissues and reveal the key events of early human morphogenesis. These include segregation of the pluripotent embryonic and extra-embryonic lineages, and morphogenetic rearrangements leading to generation of a bilaminar disc, formation of a pro-amniotic cavity within the embryonic lineage, appearance of the prospective yolk sac, and trophoblast differentiation. Using human embryos and human pluripotent stem cells, we show that the reorganization of the embryonic lineage is mediated by cellular polarization leading to cavity formation. Together, our results indicate that the critical remodelling events at this stage of human development are embryo-autonomous, highlighting the remarkable and unanticipated self-organizing properties of human embryos.

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