title: A method to recapitulate early embryonic spatial patterning in human embryonic stem cells.
abstract: Embryos allocate cells to the three germ layers in a spatially ordered sequence. Human embryonic stem cells (hESCs) can generate the three germ layers in culture; however, differentiation is typically heterogeneous and spatially disordered. We show that geometric confinement is sufficient to trigger self-organized patterning in hESCs. In response to BMP4, colonies reproducibly differentiated to an outer trophectoderm-like ring, an inner ectodermal circle and a ring of mesendoderm expressing primitive-streak markers in between. Fates were defined relative to the boundary with a fixed length scale: small colonies corresponded to the outer layers of larger ones. Inhibitory signals limited the range of BMP4 signaling to the colony edge and induced a gradient of Activin-Nodal signaling that patterned mesendodermal fates. These results demonstrate that the intrinsic tendency of stem cells to make patterns can be harnessed by controlling colony geometries and provide a quantitative assay for studying paracrine signaling in early development.
authors: 1] Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA. [2] Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA. [3].
authors: Aryeh
authors: A
authors: Warmflash
authors: 1] Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA. [2] Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA. [3].
authors: Benoit
authors: B
authors: Sorre
authors: 1] Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA. [2] Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA.
authors: Fred
authors: F
authors: Etoc
authors: Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA.
authors: Eric D
authors: ED
authors: Siggia
authors: Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA.
authors: Ali H
authors: AH
authors: Brivanlou
mesh_terms: D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology*; D054262:Gastrulation; D006801:Humans; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta