title: Molecular and functional characterizations of gastrula organizer cells derived from human embryonic stem cells.
abstract: The Spemann-Mangold organizer is the structure that provides the signals, which initiate pattern formation in the developing vertebrate embryo, affecting the main body axes. Very little is known about axial induction in the gastrulating human embryo, as research is hindered by obvious ethical restrictions. Human embryonic stem cells (hESCs) are pluripotent cells derived from the pregastrula embryo that can differentiate in culture following a program similar to normal embryonic development but without pattern formation. Here, we show that in hESC-derived embryoid bodies, we can induce differentiation of cells that harbor markers and characteristics of the gastrula-organizer. Moreover, genetic labeling of these cells enabled their purification, and the discovery of a comprehensive set of their secreted proteins, cell surface receptors, and nuclear factors characteristic of the organizer. Remarkably, transplantation of cell populations enriched for the putative human organizer into frog embryos induced a secondary axis. Our research demonstrates that the human organizer can be induced in vitro and paves the way for the study of pattern formation and the initial regulation of body axis establishment in humans.
authors.affiliation: Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Sharon
authors.forename: Ishay
authors.initials: I
authors.lastname: Mor
authors.forename: Tamar
authors.initials: T
authors.lastname: Golan-lev
authors.forename: Abraham
authors.initials: A
authors.lastname: Fainsod
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D019521:Body Patterning; D002454:Cell Differentiation / Q000502:physiology; D058732:Embryoid Bodies / Q000378:metabolism; D004627:Embryonic Induction; D053595:Embryonic Stem Cells / Q000378:metabolism*; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein / Q000096:biosynthesis; D006801:Humans; D020897:Organizers, Embryonic / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D051956:Goosecoid Protein; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins