title: Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts.
abstract: Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs.
authors: From the Department of Chemical and Biomolecular Engineering.
authors: Prasenjit
authors: P
authors: Sarkar
authors: the W. M. Keck FT-ICR Mass Spectrometry Laboratory, Department of Chemistry, and.
authors: Shan M
authors: SM
authors: Randall
authors: the W. M. Keck FT-ICR Mass Spectrometry Laboratory, Department of Chemistry, and.
authors: Timothy S
authors: TS
authors: Collier
authors: From the Department of Chemical and Biomolecular Engineering.
authors: Anthony
authors: A
authors: Nero
authors: the Department of Biochemistry, North Carolina State University, Raleigh, North Carolina 27695.
authors: Teal A
authors: TA
authors: Russell
authors: the W. M. Keck FT-ICR Mass Spectrometry Laboratory, Department of Chemistry, and.
authors: David C
authors: DC
authors: Muddiman
authors: From the Department of Chemical and Biomolecular Engineering, bmrao@ncsu.edu.
authors: Balaji M
authors: BM
authors: Rao
mesh_terms: D028341:Activins / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D019175:DNA Methylation; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics; D006801:Humans; D055457:Nodal Protein / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D036388:Ephrin-B2; C526007:NODAL protein, human; D055457:Nodal Protein; D028341:Activins
keywords: Activin; Activin/Nodal Signaling; BMP Signaling; Bone Morphogenetic Protein (BMP); Differentiation; ELF5; Embryonic Stem Cell; Human Embryonic Stem Cells; Trophoblast