Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA144037 | ENA |
REPOSITORIES: ENA
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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 M-NM-2hCG 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.
2012-10-17 | E-GEOD-30125 | biostudies-arrayexpress
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
Project description:NANOG has emerged as a central gatekeeper of pluripotency. Here we show that as human embryonic stem (ES) cells exit the pluripotent state, NANOG can play a key role in determining lineage outcome. It has previously been reported that BMPs can induce differentiation of human ES cells into extraembryonic lineages. Here we report that FGF2 switches BMP4 induced differentiation outcome to mesendoderm, characterized by the uniform expression of T (brachyury) and other primitive streak markers. Blocking the MEK-ERK pathway either by chemical inhibitors or by an ERK-specific phosphatase (DUSP6) blocks the FGF2-mediated lineage switch. Active MEK-ERK signaling prolongs NANOG expression during BMP-induced differentiation. Forced NANOG expression results in FGF independent BMP4 induction of mesendoderm, and knockdown of NANOG greatly reduces T induction. Together, our results demonstrate that FGF2 signaling switches the outcome of BMP4 induced differentiation of human ES cells by maintaining NANOG levels through the MEK-ERK pathway. There are three sets of expression data. Set 1 (14 samples) is 5day human ES cells (H1) differentiated with different concentrations of BMP4, in the presence or absence of FGF2. Set 2 (14 samples) is 50ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2. Set 3 (22 samples) is 5ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2.
2011-03-03 | E-GEOD-25973 | biostudies-arrayexpress
Project description:Here we identify conditions that efficiently drive specification of primed induced pluripotent stem cells to trophectoderm, named Trophoblast Stem Cell (TS). iPS-derived-TS cells share transcriptional, morphological and functional characteristics with human ex vivo cytotrophoblasts including transcriptional activation of human endogenous retroviruses, expression of COVID-19 associated host factors and the ability to generate multinucleated syncytiotrophoblasts with a large fusion index. At high densities in 5% O2, iPS-derived-TS cells form villi-like structures and express extravillous and syncytiotrophoblast proteins HCG-β, HLA-G. To define the molecular changes associated with specification, we compare temporal single cell RNAseq analysis under three separate conditions: 1) BMP4, 2) BMP4 and inhibition of Wnt, 3) Trophoblast Stem cell condition (TS) activation of EGF and Wnt, inhibition of TGFbeta, HDAC and ROCK signaling.
2021-10-02 | E-MTAB-9526 | biostudies-arrayexpress
Project description:NANOG has emerged as a central gatekeeper of pluripotency. Here we show that as human embryonic stem (ES) cells exit the pluripotent state, NANOG can play a key role in determining lineage outcome. It has previously been reported that BMPs can induce differentiation of human ES cells into extraembryonic lineages. Here we report that FGF2 switches BMP4 induced differentiation outcome to mesendoderm, characterized by the uniform expression of T (brachyury) and other primitive streak markers. Blocking the MEK-ERK pathway either by chemical inhibitors or by an ERK-specific phosphatase (DUSP6) blocks the FGF2-mediated lineage switch. Active MEK-ERK signaling prolongs NANOG expression during BMP-induced differentiation. Forced NANOG expression results in FGF independent BMP4 induction of mesendoderm, and knockdown of NANOG greatly reduces T induction. Together, our results demonstrate that FGF2 signaling switches the outcome of BMP4 induced differentiation of human ES cells by maintaining NANOG levels through the MEK-ERK pathway.
2011-03-03 | GSE25973 | GEO
Project description:The transition from progenitor to differentiated cells is critical for successful organogenesis; subtle alterations in this process can lead to developmental disorders. The anterior heart field (AHF) encompasses a niche in which cardiac progenitors maintain their multipotent and undifferentiated nature by signals from the surrounding tissues, which thus far have been poorly defined. Using systems biology approaches and perturbations of signaling molecules in chick embryos, we revealed a tight crosstalk between the bone morphogenic protein (BMP) and fibroblast growth factor (FGF) signaling pathways within the AHF: BMP4 promotes myofibrillar gene expression and cardiomyocyte contractions, by blocking FGF signaling. Furthermore, inhibition of the FGF-ERK pathway is both sufficient and necessary for these processes, suggesting that FGF signaling blocks premature differentiation of cardiac progenitors in the AHF. Investigating the molecular mechanisms downstream to BMP signaling revealed that BMP4 induced a set of neural crest-related genes; including MSX1, which was sufficient to induce cardiomyocyte differentiation. We suggest that BMP and FGF signaling pathways act via inter- and intra-regulatory loops in multiple tissues, to coordinate the balance between proliferation and differentiation of cardiac progenitors. Splanchnic mesoderm (AHF) explants were dissected and cultured for 0, 3, 12 or 24 hrs on a collagen drop covered with 0.5 ml of dissection medium (10% Fetal Calf Serum, chick embryo extract 2.5% and pen/strep 0.5% in MEM medium). 12 hour time point was used as a duplicate. In all samples, there was control plus BMP4: human recombinant BMP4 (Sigma, 200 ng/mL), which was added to the explant dissection medium.
2010-08-01 | E-GEOD-19698 | biostudies-arrayexpress
Project description:Gene expression microarray analysis of hESCs treated with BMP4 in chemically-defined medium, with and without inhibitors of Activin and FGF signalling (which maintain pluripotency), to investigate the induction of extra-embryonic tissue (trophectoderm) differentiation by BMP signalling.
2009-07-31 | E-MEXP-1192 | biostudies-arrayexpress
Project description:Trophoblast is the primary epithelial cell type in the placenta, a transient organ required for proper fetal growth and development. We have identified a CDX2+/p63+ cytotrophoblast (CTB) subpopulation in the early post-implantation human placenta, which is significantly reduced later in gestation. CTB differentiate into different trophoblast subtypes, which are responsible for gas/nutrient exchange (syncytiotrophoblast/STB) and invasion and maternal vascular remodeling (extravillous trophoblast/EVT). Study of early human placental development is severely hampered by lack of a representative trophoblast stem cell (TSC) model, with the capacity for self-renewal and the ability to differentiate into both STB and EVT. We describe a reproducible protocol, using defined media containing BMP4, by which human embryonic stem cells (hESC) can be differentiated into CDX2+/p63+ CTB-like cells. These cells can be replated to further differentiate into STB- and EVT-like cells, based on marker expression, hormone secretion and invasive ability. Differentiation of hPSC-derived CTB in hypoxia leads to reduced hCG secretion and STB-associated gene expression, instead inducing EVT differentiation in a hypoxia-inducible factor-dependent manner. Human embryonic stem cells (hESC) (WA09/H9) were maintained on Geltrex-coated plates (BD Biosciences ) in StemPro (Thermo Fisher) + bFGF (12 ng/ml). Undifferentiated hESC (D-2) were switched to minimal media (EMIM (Erb et al., 2011) containing KO DMEM/F12 (Gibco), 1% Insulin-Transferrin-Selenium Mix (Sigma-Aldrich), 1% NEAA (Gibco), 2mM L-Glutamine (Corning), 0.1mM 2-mercaptoethanol (Gibo), and 2% BSA (Gemini Bio Products)) for 2 days then treated with BMP4 (StemRD, 10ng/ml) for 3 days in minimal media+BMP4 (D3). At D3, cells were replated onto Geltrex in Feeder Conditioned Media +BMP4 and cultured in normoxia (20% O2) or hypoxia (2% O2) for 2 days (D3+2) to assess the effect of hypoxia. Cells were infected with lentiviral shRNA for shScramble (control) or shARNT, the beta subunit of the Hypoxia Inducible Factor (HIF) complex to assess the effect of ARNT knockdown. Each sample includes biological triplicates.
2016-06-16 | E-GEOD-76090 | biostudies-arrayexpress
Project description:Analysis of the effects of three members of the FGF family (FGF1, FGF2 and FGF9) and bone morphogenic protein 4 (BMP4) on myelinating cultures generated from dissociated embryonic spinal cord. The results of both immediate (24 hours, T1 (24 hrs)) and long term treatments (10days, T2) give insights into the cumulative effects of sustained FGF and BMP mediated signal transduction in the pathogenesis of demyelinating diseases.
2015-02-18 | GSE52753 | GEO
Project description:BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a ΔNp63+ cytotrophoblast stem cell state
| PRJNA213715 | ENA