Transcriptomics

Dataset Information

2

FGF inhibition directs BMP4-mediated differentiation of Human Embryonic Stem Cells to syncytiotrophoblast


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 βhCG 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. Human embryonic Stem Cells (hESCs) were treated under defined conditions (N2B27) with BMP4 (B), SB431542 (SB) (ACTIVIN/NODAL inhibitor), SU5402 (SU) (FGFR1 inhibitor), FGF2 (F) either alone or in various combinations as mentioned, followed by isolation of total RNA.

ORGANISM(S): Homo sapiens  

SUBMITTER: James Adjaye   Raghu Bhushan  Hans Lehrach  smita sudheer  Smita Sudheer  Beatrix Fauler 

PROVIDER: E-GEOD-30125 | ArrayExpress | 2012-10-17

SECONDARY ACCESSION(S): GSE30125PRJNA144037

REPOSITORIES: GEO, ArrayExpress

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Publications

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

Sudheer Smita S   Bhushan Raghu R   Fauler Beatrix B   Lehrach Hans H   Adjaye James J  

Stem cells and development 20120806 16


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  ...[more]

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