title: Self-organization of the human embryo in the absence of maternal tissues.
abstract: 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.
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Marta N
authors.initials: MN
authors.lastname: Shahbazi
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jedrusik
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Sanna
authors.initials: S
authors.lastname: Vuoristo
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Recher
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Hupalowska
authors.affiliation: 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.
authors.forename: Virginia
authors.initials: V
authors.lastname: Bolton
authors.affiliation: Human Embryo and Stem Cell Laboratory, Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK.
authors.forename: Norah N M
authors.initials: NNM
authors.lastname: Fogarty
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, NG8 6PZ, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Campbell
authors.affiliation: 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.
authors.forename: Liani
authors.initials: L
authors.lastname: Devito
authors.affiliation: 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.
authors.forename: Dusko
authors.initials: D
authors.lastname: Ilic
authors.affiliation: 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.
authors.forename: Yakoub
authors.initials: Y
authors.lastname: Khalaf
authors.affiliation: Human Embryo and Stem Cell Laboratory, Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK.
authors.forename: Kathy K
authors.initials: KK
authors.lastname: Niakan
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, NG8 6PZ, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Fishel
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience; Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D010064:Embryo Implantation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D009024:Morphogenesis / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology*; D015017:Yolk Sac / Q000378:metabolism*