02086nas a2200313   4500000000100000000000100001008004100002260001200043653001500055653002500070653002800095100001300123700001500136700001300151700001600164700002600180700001200206700002300218700002400241700002200265700002300287700001600310245008300326856005400409300001200463490000800475520127500483022001401758       2019                            d  c2019-0910aEmbryology10aEmbryonic stem cells10aStem-cell biotechnology1 aYi Zheng1 aXufeng Xue1 aYue Shao1 aSicong Wang1 aSajedeh Nasr Esfahani1 aZida Li1 aJonathon M. Muncie1 aJohnathon N. Lakins1 aValerie M. Weaver1 aDeborah L. Gumucio1 aJianping Fu00aControlled modelling of human epiblast and amnion development using stem cells  uhttps://www.nature.com/articles/s41586-019-1535-2  a421-4250 v5733 aEarly human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning1. Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence2,3 and limited accessibility to human embryo samples. Here we report that human pluripotent stem cells (hPSCs) in a microfluidic device recapitulate, in a highly controllable and scalable fashion, landmarks of the development of the epiblast and amniotic ectoderm parts of the conceptus, including lumenogenesis of the epiblast and the resultant pro-amniotic cavity, formation of a bipolar embryonic sac, and specification of primordial germ cells and primitive streak cells. We further show that amniotic ectoderm-like cells function as a signalling centre to trigger the onset of gastrulation-like events in hPSCs. Given its controllability and scalability, the microfluidic model provides a powerful experimental system to advance knowledge of human embryology and reproduction. This model could assist in the rational design of differentiation protocols of hPSCs for disease modelling and cell therapy, and in high-throughput drug and toxicity screens to prevent pregnancy failure and birth defects.  a1476-4687