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Journal Article

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

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons50581

Sudheer,  Smita
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;
Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50148

Fauler,  Beatrix
Imaging/Electron Microscopy (Head: Rudi Lurz/Thorsten Mielke), Scientific Service (Head: Manuela B. Urban), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50054

Adjaye,  James
Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Sudheer.pdf
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Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-F0A3-C
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.