title: Self-organization of the in vitro attached human embryo.
abstract: Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Deglincerti
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Gist F
authors.initials: GF
authors.lastname: Croft
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Pietila
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Physiology Building, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
authors.affiliation: Center for Studies in Physics and Biology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Siggia
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
mesh_terms: D000650:Amnion / Q000166:cytology / Q000196:embryology; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D020964:Embryo Loss / Q000473:pathology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000166:cytology* / Q000196:embryology*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology / Q000473:pathology / Q000637:transplantation; D005855:Germ Layers / Q000166:cytology / Q000196:embryology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008954:Models, Biological; D013045:Species Specificity; D014327:Trophoblasts / Q000166:cytology; D015017:Yolk Sac / Q000166:cytology / Q000196:embryology