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  FGF inhibition directs BMP4-mediated differentiation of human embryonic stem cells to syncytiotrophoblast

Sudheer, S., Bhushan, R., Fauler, B., Lehrach, H., & Adjaye, J. (2012). FGF inhibition directs BMP4-mediated differentiation of human embryonic stem cells to syncytiotrophoblast. Stem Cells and Development, 21(16), 2987-3000. doi:10.1089/scd.2012.0099.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F0A3-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F0A4-A
Genre: Journal Article

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© 2012 Mary Ann Liebert, Inc. publishers
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 Creators:
Sudheer, Smita1, 2, Author              
Bhushan, Raghu3, Author
Fauler, Beatrix4, Author              
Lehrach, Hans5, Author              
Adjaye, James6, Author              
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
2Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, ou_persistent22              
3Institute for Chemistry and Biochemistry, Freie Universität Berlin, ou_persistent22              
4Imaging/Electron Microscopy (Head: Rudi Lurz/Thorsten Mielke), Scientific Service (Head: Manuela B. Urban), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
5Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
6Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479654              

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Free keywords: Activins/metabolism Animals Autocrine Communication/drug effects/genetics Benzamides/pharmacology Bone Morphogenetic Protein 4/*pharmacology Cell Differentiation/*drug effects/genetics Cell Fusion Cell Line Chorionic Gonadotropin, beta Subunit, Human/metabolism Dioxoles/pharmacology Embryonic Stem Cells/*cytology/drug effects/metabolism Endoderm/cytology/drug effects/metabolism Female Fibroblast Growth Factors/*antagonists & inhibitors/metabolism Gene Expression Regulation/drug effects Homeodomain Proteins/genetics/metabolism Humans Mesoderm/cytology/drug effects/metabolism Mice Models, Biological Nodal Protein/antagonists & inhibitors/metabolism Placenta/drug effects/metabolism Pregnancy Pyrroles/pharmacology Signal Transduction/drug effects/genetics Trophoblasts/*cytology/drug effects/metabolism Wnt Proteins/metabolism
 Abstract: Bone morphogenetic protein (BMP) signaling is known to support differentiation of human embryonic stem cells (hESCs) into mesoderm and extraembryonic lineages, whereas other signaling pathways can largely influence this lineage specification. Here, we set out to reinvestigate the influence of ACTIVIN/NODAL and fibroblast growth factor (FGF) pathways on the lineage choices made by hESCs during BMP4-driven differentiation. We show that BMP activation, coupled with inhibition of both ACTIVIN/NODAL and FGF signaling, induces differentiation of hESCs, specifically to betahCG hormone-secreting multinucleated syncytiotrophoblast and does not support induction of embryonic and extraembryonic lineages, extravillous trophoblast, and primitive endoderm. It has been previously reported that FGF2 can switch BMP4-induced hESC differentiation outcome to mesendoderm. Here, we show that FGF inhibition alone, or in combination with either ACTIVIN/NODAL inhibition or BMP activation, supports hESC differentiation to hCG-secreting syncytiotrophoblast. We show that the inhibition of the FGF pathway acts as a key in directing BMP4-mediated hESC differentiation to syncytiotrophoblast.

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Language(s): eng - English
 Dates: 2012-08-062012-11-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1089/scd.2012.0099
 Degree: -

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Title: Stem Cells and Development
  Other : Stem Cells Dev.
Source Genre: Journal
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Publ. Info: Larchmont, NY : Mary Ann Liebert, Inc.
Pages: - Volume / Issue: 21 (16) Sequence Number: - Start / End Page: 2987 - 3000 Identifier: ISSN: 1547-3287
CoNE: /journals/resource/954925275493