Shahbazi Marta N, Jedrusik Agnieszka, Vuoristo Sanna, Recher Gaelle, Hupalowska Anna, Bolton Virginia, Fogarty Norah N M, Campbell Alison, Devito Liani, Ilic Dusko, Khalaf Yakoub, Niakan Kathy K, Fishel Simon, Zernicka-Goetz Magdalena
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.
Nat Cell Biol. 2016 Jun;18(6):700-708. doi: 10.1038/ncb3347. Epub 2016 May 4.
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.
植入时人类胚胎的重塑对于成功妊娠必不可少。然而,由于困扰这一发育阶段研究的实验障碍,它一直很神秘。在这里,我们建立了一个体外系统,在没有母体组织的情况下培养人类胚胎直至植入阶段,并揭示早期人类形态发生的关键事件。这些事件包括多能胚胎和胚外谱系的分离,以及导致双胚层盘形成的形态发生重排、胚胎谱系内羊膜腔的形成、预期卵黄囊的出现和滋养层分化。利用人类胚胎和人类多能干细胞,我们表明胚胎谱系的重组是由导致腔形成的细胞极化介导的。总之,我们的结果表明,人类发育这一阶段的关键重塑事件是胚胎自主的,突出了人类胚胎显著且出人意料的自组织特性。