FGF Inhibition Directs BMP4-Mediated Differentiation of Human Embryonic Stem Cells to Syncytiotrophoblast
Publication: Stem Cells and Development
Volume 21, Issue Number 16
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.
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Information & Authors
Information
Published In
Stem Cells and Development
Volume 21 • Issue Number 16 • November 1, 2012
Pages: 2987 - 3000
PubMed: 22724507
Copyright
Copyright 2012, Mary Ann Liebert, Inc.
History
Published in print: November 1, 2012
Published ahead of print: 6 August 2012
Published online: 22 June 2012
Accepted: 20 June 2012
Received: 24 February 2012
Authors
Author Disclosure Statement
No competing financial interests exist.
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