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Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm

ABSTRACT: Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm

PROVIDER: PRJNA555431 | ENA |

REPOSITORIES: ENA

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Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm.

Project description: Not available

| S-EPMC8050086 | biostudies-literature

Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm

Project description:This dataset includes the RNA sequencing of five replicates of the undifferentiated hESC subline VUB03_S2, which shows impaired mesendoderm induction, and 14 WT samples from GSE116372.

2021-04-06 | GSE134454 | GEO

BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage

Project description:Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1 establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.

2023-05-03 | GSE168580 | GEO

Methylation analysis of human embryonic stem cells (hESCs), hESC-derived splanchnic mesoderm and hESC-derived mesothelium (mesenchymal form)

Project description:Genome wide DNA methylation profiling of hESC-derived mesothelium (MesoT), hESCs and hESC-derived splanchnic mesoderm (SplM) compared to primary human tissue samples. The Illumina Infinium HumanMethylation450 BeadChip kit was used to obtain DNA methylation profiles across approximately 450,000 methylation sites. Samples include 2 WA09 hESCs, 2 hESC-derived splanchnic mesoderm and 3 hESC-derived mesothelium replicates.

2018-10-06 | GSE116754 | GEO

Synergism between Activin A and BMP4 in directing the formation of definitive endoderm in human embryonic stem cells

Project description:Human embryonic stem cells (HESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. Here, we show that combining a second related ligand, BMP4, in combination with Activin A yields 15 to 20% more DE as compared to Activin A alone. The addition of recombinant BMP4 accelerates the downregulation of pluripotency factors, particularly SOX2, and results in upregulation of endogenous BMP2 and BMP4, which in turn leads to elevated levels of phospho-SMAD1/5/8 over the next three days of differentiation. Combined Activin A and BMP4 treatment also leads to an increase in the expression of DE genes CXCR4, SOX17 and FOXA2 when compared to Activin A addition alone. Comparative microarray studies between DE cells harvested on day 3 of differentiation further reveal a novel set of genes upregulated in response to initial BMP4 exposure. Several of these, including APLNR, LRIG3, MCC and LZTS1, are expressed either in the mouse primitive streak, the site of DE formation, or in nascent DE itself. Thus, this synergism between Activin A and BMP4 during the in vitro differentiation of HESC into DE suggests a complex interplay between BMP and Activin/Nodal signaling during the in vivo allocation and expansion of the endoderm lineage. 3 biological replicates of 3-day ActivinA treated HES3 human stem cell culture were compared to 3-day ActivinA+Bmp4 treated HES3 human stem cell culture and observed for differential genes expression

2011-11-10 | E-GEOD-30630 | biostudies-arrayexpress

Transcriptome profiling of hESC-derived endoderm progenitors by single-cell RNA-seq

Project description:In this study, we characterised transcriptomes of hESC-derived transient anterior definitive endoderm (ADE) and expanding ventral foregut (VFG) culture by single-cell sequencing. We also examined the effect of BMP4 withdrawal and FGF2 stimulation in the VFG culture.

2022-11-15 | GSE188362 | GEO

Synergism between Activin A and BMP4 in directing the formation of definitive endoderm in human embryonic stem cells

2011-11-10 | GSE30630 | GEO

BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage

Project description:BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage

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Characterization of Definitive Endoderm formation from HESC and iPSC lines by Microarray analysis

Project description:HESC-H9 and iPSC lines 3.5, 3.6 and 3.12 were analyzed using Affymetrix microarray before and after Definitive Endoderm (DE) formation. DE was induced using the ActivinA differentiation protocol described by D'Amour et al., 2006 (PMID: 16258519) Clustering analysis of transcripts that were differentially regulated during DE formation indicated that iPSC lines 3.5 and 3.12 differentiate in manner that is highly similar to HESC-H9 cells iPSC line 3.6 had a more divergent transcriptional profile.

2010-12-25 | GSE25557 | GEO

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

Project description: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.

2012-10-17 | GSE30125 | GEO

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