title: Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro.
abstract: Mammalian embryogenesis requires intricate interactions between embryonic and extraembryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combined mouse embryonic stem cells (ESCs) and extraembryonic trophoblast stem cells (TSCs) in a three-dimensional scaffold to generate structures whose morphogenesis is markedly similar to that of natural embryos. By using genetically modified stem cells and specific inhibitors, we show that embryogenesis of ESC- and TSC-derived embryos-ETS-embryos-depends on cross-talk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extraembryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell types resemble those of natural 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: Sarah Ellys
authors.identifier: 0000-0002-1571-2399
authors.initials: SE
authors.lastname: Harrison
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3DY, UK.|Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, 07070, Turkey.
authors.forename: Berna
authors.identifier: 0000-0001-5834-5819
authors.initials: B
authors.lastname: Sozen
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: Neophytos
authors.identifier: 0000-0003-4338-5847
authors.initials: N
authors.lastname: Christodoulou
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: Christos
authors.identifier: 0000-0001-8516-9195
authors.initials: C
authors.lastname: Kyprianou
authors.affiliation: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3DY, UK. mzg@mole.bio.cam.ac.uk.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000502:physiology*; D054262:Gastrulation; D005855:Germ Layers; D066298:In Vitro Techniques; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development; D051379:Mice; D008954:Models, Biological; D054457:Tissue Scaffolds; D014327:Trophoblasts / Q000502:physiology*; D060449:Wnt Signaling Pathway