Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
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ABSTRACT:
PROVIDER: PRJNA947968 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23949047_1.fastq.gz | Fastqsanger.gz | |||
| SRR23949047_2.fastq.gz | Fastqsanger.gz | |||
| SRR23949048_1.fastq.gz | Fastqsanger.gz | |||
| SRR23949048_2.fastq.gz | Fastqsanger.gz | |||
| SRR23949049_1.fastq.gz | Fastqsanger.gz |
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Project description:The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal, and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but which mesodermal cell types depend on FGF signaling is not precisely known. It is also not clear how FGF signaling modulates the activity of orthogonal signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations with single cell resolution. We identify opposing functions of BMP and FGF, and map the boundary between FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgfs while repressing Bmp ligands. This intercellular positive autoregulation of FGF signaling coupled to the repression of BMP signaling may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems.
2023-03-24 | GSE228061 | GEO
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2020-06-23 | GSE149335 | GEO
Project description:The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but how FGF shapes mesodermal cell type diversity is not precisely known. It is also not clear how FGF signaling integrates with the activity of other signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations at single-cell resolution. We identify opposing functions of BMP and FGF, and map FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgf genes while repressing Bmp ligand genes. This positive autoregulation of FGF signaling, coupled with the repression of BMP signaling, may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems.
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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:Caudal somites are generated from a pool of progenitor cells located in the tailbud region. These progenitor cells form the presomitic mesoderm that gradually differentiates into somites under the action of the segmentation clock. The signals responsible for tailbud mesoderm progenitor pool maintenance during axial elongation are still elusive. Here, we show that Bmp signaling is sufficient to activate the entire mesoderm progenitor gene signature in primary cultures of caudal mesoderm cells. Bmp signaling acts through the key regulatory genes Brachyury (T) and Nkx1-2 and contributes to the activation of several other regulators of the mesoderm progenitor gene network. In the absence of Bmp signaling, tailbud mesoderm progenitor cells acquire aberrant gene expression signatures of the heart, blood, muscle and skeletal embryonic lineages. Treatment of embryos with the Bmp inhibitor Noggin confirmed the requirement for Bmp signaling for normal Brachyury expression and the prevention of abnormal lineage marker activation. Together, these results identify Bmp signaling as a non-cell autonomous signal necessary for mesoderm progenitor cell homeostasis.
2017-07-25 | GSE101810 | GEO
Project description:Among the three embryonic germ layers, mesoderm plays a central role in the establishment of the vertebrate body plan. Mesoderm is specified by secreted signaling proteins from the FGF, Nodal, BMP and Wnt families. No new classes of extracellular mesoderm-inducing factors have been identified in more than two decades. Here we show that the Xenopus pinhead (pnhd) gene encodes a novel secreted protein that activates specific mesodermal markers in presumptive ectoderm. We demonstrate that Pnhd is required for the specification of a subset of embryonic mesoderm in vivo. RNA sequencing revealed that many transcriptional targets of Pnhd are shared with those of the FGF pathway. Pnhd signaling involves active FGF but not Wnt receptors and is accompanied by Erk1 phosphorylation. We propose that Pnhd operates in the marginal zone to specify mesodermal progenitors via an FGF receptor-dependent mechanism.
2020-05-15 | GSE143795 | 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.
2010-08-01 | GSE19698 | GEO
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: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.
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