title: Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas.
abstract: Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83-01/PD173074; BAP treatment). During differentiation, areas emerge within the colonies with the biochemical and morphological features of syncytiotrophoblast (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and larger syncytial sheets displaying the expected markers of STB can be obtained by differential filtration of dispersed colonies through nylon strainers. RNA-seq analysis of these fractions has allowed them to be compared with cytotrophoblasts isolated from term placentas before and after such cells had formed syncytia. Although it is clear from extensive gene marker analysis that both ESC- and placenta-derived syncytial cells are trophoblast, each with the potential to transport a wide range of solutes and synthesize placental hormones, their transcriptome profiles are sufficiently dissimilar to suggest that the two cell types have distinct pedigrees and represent functionally different kinds of STB. We propose that the STB generated from human ESCs represents the primitive syncytium encountered in early pregnancy soon after the human trophoblast invades into the uterine wall.
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, MO 65211;
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yabe
authors.affiliation: Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211;
authors.forename: Andrei P
authors.initials: AP
authors.lastname: Alexenko
authors.affiliation: Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211; Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan;
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Amita
authors.affiliation: Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211;
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, MO 65211;
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213;
authors.forename: Yoel
authors.identifier: 0000-0003-2969-6737
authors.initials: Y
authors.lastname: Sadovsky
authors.affiliation: Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211;
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ezashi
authors.affiliation: Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211; Department of Biochemistry, University of Missouri, Columbia, MO 65211 robertsrm@missouri.edu.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Roberts
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D000066449:Human Embryonic Stem Cells; D006801:Humans; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D055415:Bone Morphogenetic Protein 4
keywords: BMP4; RNA-seq; human pluripotent stem cells; syncytiotrophoblast; trophoblast