Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway

ABSTRACT: In this study, we investigated the effect of bone morphogenetic protein 4 and 6 (BMP4 and BMP6) on transcriptional regulation and intracellular signaling of adult murine stem cells (MuSCs) using RNA-sequencing, RNA-expression arrays, pathway-specific qPCR arrays, and Cleavage Under Targets and Tagmentation (CUT&Tag). Freshly MACS-isolated or FACS sorted MuSCs were grown for 48 to 72 hours, kept serum deprived for 6 hours and then stimulated with BMP4 or BMP6. Intrinsic BMPs were optionally removed from the medium during serum deprivation by adsorption to soluble Bone Morphogenetic Protein Receptor Type 1A (sBMPR1A). BMP4 or BMP6 addition resulted in a rapid increase in Id1-expression, a "classic" BMP target gene, which peaked after one hour. This proportional increase was much more pronounced after removal of BMPs from serum-free medium by sBMPR1A, suggesting that MuSCs secrete BMPs cell-autonomously. BMP4 kept MuSCs longer in Pax7-positive state. As expected, stimulation by BMP4 and BMP6 resulted in a significant increase in transcription of BMP-target genes (Dlx2 => 6-fold, Fos, Smad7, Gdf5, Id1, Junb, Serpine, Nog), but also a strong increase in transcription for Notch pathway genes (Hes1 => 4.9-fold, Jag1, Jag2, Lfng). Our results suggest that the rapid expression of genes encoding Notch signaling components is due to direct BMP signaling and that BMP signaling maintains the muscle MuSC pool, possible via regulation of Hes1 expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE159594 | GEO | 2023/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The effect of BMP4/6 stimulation on adult muscle stem cells (MuSC)

Project description:Muscle development and regeneration strongly depends on extracellular cues and growth factors, which are taken up by muscle stem cells and guide them either towards proliferation and fusion or towards quiescence. Here we investigated the effect of bone morphogenetic protein (BMP) signaling on Pax7 positive adult muscle stem cells of the mouse. We discovered a cross talk between the BMP- and NOTCH-signalling pathways, leading to high upregulation upon BMP4/BMP6-stimulation of Hes1 mRNA which is a key component of the NOTCH-siganling pathway.

2023-10-01 | GSE127798 | GEO

BMP/Taz-Hippo signaling modulates VEGF-mediated angiogenesis

Project description:The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.

2020-10-07 | GSE82106 | GEO

Expression profile of early stage druing induced pluripotency regulated by BMP/FBS

Project description:FBS and BMP influence the somatic reprogramming induced by Oct4/Sox2/Klf4/c-Myc similarly. Bone morphogenetic proteins (BMPs) are abundant in serum and activate Smad1/5/8 to regulated target genes. BMPs play a important role in ES self-renewal, neurogenesis, osteogenesis, angiogenesis. We performed this experiment for identify what targets are regulated by BMPs and FBS.

2009-12-23 | GSE19604 | GEO

Gene Expression Profile identify a role for cyclooxygenase 2-depedent prostinoid generation in BMP6-induced

Project description:The bone morphogenetic protein (BMP) family of proteins participates in an underappreciated signaling pathway involved in regulating angiogensis in physiological and pathological conditions. Microarray profiles of BMP-responsive genes in the endothelium performed by our lab suggest important roles for cyclooxygenase-2 (Cox2) as a potential downstream regulator of BMP-induced angiogenesis. Cox2 is upregulated by BMP6 at both mRNA and protein levels. Inhibition of Cox2 blocks BMP6 induced endothelial cell proliferation, migration and tube formation activity. Microvessel outgrowth stimulated by BMP6 also required Cox2 activity. These results strongly support that Cox2 is an important downstream target for BMP6, and that prostaniod synthesis is essential for BMP6 induced endothelial cell activation. This further suggests that our microarray data is a reliable tool to identify unkown BMP6 targets in angiogenesis. Keywords: BMP, angiogenesis, Cox2, MEC

2006-12-31 | GSE4909 | GEO

Expression data from untreated vs. BMP4-treated cultured wild-type and MuSK null muscle cells (myoblasts and myotubes)

Project description:Bone morphogenic proteins (BMPs) function in virtually all tissues with cell-type specific outcomes. Since there are a relatively small number of BMP receptors this exquisite signaling specificity requires additional molecules to regulate the output of this pathway. We demonstrated that the receptor tyrosine kinase MuSK that is selectively expressed in muscle and plays a critical role in synapse formation and maintenance binds to BMP4 and related BMPs. Since BMPs regulate the transcription of a set of genes, we performed microarrays for wild-type and MuSK null muscle cells to test if MuSK regulates BMP responses in muscle cells. We shought to determine if MuSK regulates BMP responses in muscle cells and if the cell context made any difference in MuSK regulation of BMP pathway. To test this, expression profiles of untreated vs. BMP4-treated undifferentiated myoblast and differentiated myotube cultures were generated for both wild-type and MuSK-null genotypes. All conditions were done in triplicates. In total 24 arrays were analyzed.

2015-08-03 | E-GEOD-59567 | biostudies-arrayexpress

BMP9_BMPR2_PAEC_BOEC

Project description:Human pulmonary arterial endothelial cells (PAECs) and blood outgrowth endothelial cells (BOECs) from healthy subjects were stimulated with BMP9, BMP2 or BMP6. and assessed for changes in gene transcription by microarray. Unlike BMP2 and BMP6, which had negligible impacts on gene expression, BMP9 induced the differential regulation of 1883 genes (adjusted P value < 0.05), including several key components of canonical BMP signaling such as ID1, ID2 and BMPR2.

2015-06-15 | E-MTAB-2495 | biostudies-arrayexpress

Quantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron

Project description:Iron induces hepcidin by activating bone morphogenetic protein (BMP)6-SMAD signaling. Liver endothelial cells (LECs) produce BMP6, but the molecular mechanisms are incompletely understood. To address this, we performed proteomics and RNA-sequencing on LECs from iron-adequate and iron-loaded mice. Gene set enrichment analysis identified transcription factors activated by high iron, including Nrf-2, which was previously reported to contribute to BMP6 regulation, and proto-oncogene c-Jun (encoded by Jun). Jun knockdown blocked Bmp6, but not Nrf-2 pathway, induction by iron in LEC cultures. Moreover, chromatin immunoprecipitation of mouse livers showed iron-dependent c-Jun binding to predicted sites in Bmp6 regulatory regions. Finally, c-Jun inhibitor blunted induction of Bmp6 and hepcidin, but not Nrf-2 activity, in iron-loaded mice. However, Bmp6 expression and iron parameters were unchanged in endothelial Jun knockout mice. Our data suggest that c-Jun participates in iron-mediated BMP6 regulation independent of Nrf-2, though the mechanisms may be redundant and/or multifactorial.

2023-12-28 | PXD039830 | Pride

Human breast cancer cell lines: vehicle vs. BMP4 incubation

Project description:Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of growth factors. They are known for their roles in regulation of osteogenesis and developmental processes and, in recent years, evidence has accumulated of their crucial functions in tumor biology. BMP4, in particular, has been implicated in breast cancer. However, little is known about BMP target genes in the context of tumor. We therefore explored the effects of BMP4 treatment on global gene transcription in five breast cancer cell lines during a 6-point time series. Data analysis included hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data. BMP4 had a strong effect on gene expression. The cellular functions most strongly affected were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, with regulation of gene expression and signal transduction leading to changes in metabolism and cell proliferation. Hierarchical clustering revealed distinct differences in the response of individual cell lines to BMP4, but also highlighted a synexpression group of genes. Finally, this study provides a list of potential novel BMP target genes relevant in breast cancer. Two-condition experiment, vehicle-treated vs. BMP4-treated. Five cell lines were tested at six time points each, what makes a total of 30 samples. RNA samples from three biological replicates were pooled before hybridization.

2012-03-22 | E-GEOD-31603 | biostudies-arrayexpress

RNA-sequencing signatures of liver endothelial cells from iron-adequate and iron-loaded mice

Project description:Iron induces hepcidin by activating bone morphogenetic protein (BMP)6-SMAD signaling, which is critical for regulation of systemic iron homeostasis. High iron levels induce BMP6 production in liver endothelial cells, but the molecular mechanisms by which iron regulates BMP6 are incompletely understood. To address this, we performed RNA-sequencing on sorted liver endothelial cells from iron-adequate and iron-loaded mice.

2023-12-25 | GSE223871 | GEO

Gene expression profiling in salivary glands by BMP-2.

Project description:Bone Morphogenetic Protein (BMP), a bone induction factor, belongs to the TGF-β superfamily, and more than 15 types of BMP family molecules have been reported in mammals. They are known to enhance osteoblast differentiation and their osteogenic effects, and also promote differentiation into chondrocytes. While the effects of BMPs on hard tissues are varied and numerous reports have been reported, only a few have reported the effects of BMPs on salivary glands. The aim of this study was to investigate the function of BMP-2 in the formation of salivary glands.

2023-08-18 | GSE240456 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data