Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-beta/activin/nodal signalling inhibition

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Koel , M , Vosa , U , Krjutskov , K , Einarsdottir , E , Kere , J , Tapanainen , J , Katayama , S , Ingerpuu , S , Jaks , V , Stenman , U-H , Lundin , K , Tuuri , T & Salumets , A 2017 , ' Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-beta/activin/nodal signalling inhibition ' , Reproductive BioMedicine Online , vol. 35 , no. 3 , pp. 253-263 . https://doi.org/10.1016/j.rbmo.2017.06.003

Title: Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-beta/activin/nodal signalling inhibition
Author: Koel, Mariann; Vosa, Urmo; Krjutskov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres
Contributor: University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2017-09
Language: eng
Number of pages: 11
Belongs to series: Reproductive BioMedicine Online
ISSN: 1472-6483
URI: http://hdl.handle.net/10138/297902
Abstract: Several studies have demonstrated that human embryonic stem cells [hESC] can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 [BMP4] and/or inhibitors of fibroblast growth factor 2 [FGF2] and the transforming growth factor beta [TGF-beta]/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin [HCG] and its hyperglycosylated form [HCG-H] were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes [CGA, CGB and LGALS16], induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-beta/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. (C) 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Subject: bone morphogenic protein 4
fibroblast growth factor 2
human embryonic stem cell
placenta
transforming growth factor-beta
trophoblast cells
EXTRAVILLOUS TROPHOBLAST
BMP4
EXPRESSION
SWITCHES
FGF2
3123 Gynaecology and paediatrics
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