BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA669835 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12837025.fastq.gz | Fastqsanger.gz | |||
| SRR12837026.fastq.gz | Fastqsanger.gz | |||
| SRR12837027.fastq.gz | Fastqsanger.gz | |||
| SRR12837028.fastq.gz | Fastqsanger.gz | |||
| SRR12837029.fastq.gz | Fastqsanger.gz |
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Project description: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.
2023-10-01 | GSE159594 | GEO
Project description:Muscle stem cell (MuSC) activation, proliferation, self-renewal, and differentiation are tightly regulated processes that enable muscle development and regeneration without exhaustion of the stem cell pool. BMP signaling keeps MuSCs in a proliferative state and prevents their differentiation. We investigated the effect of bone morphogenetic protein 4 and 6 (BMP4 and BMP6) on transcriptional regulation and intracellular signaling of adult murine MuSCs using RNA-sequencing, RNA expression arrays, pathway-specific qPCR arrays, and Cleavage Under Targets and Tagmentation (CUT&Tag), which identifies the binding sites of transcription factors and the presence of specific histone marks with high spatial resolution. Freshly isolated MuSCs were grown for 42 to 72 hours, kept serum deprived for 6 hours, and then stimulated with BMP4/6. BMP4/6 addition resulted in a rapid increase in Inhibitor of DNA binding 1 (Id1)-expression, a typical BMP target gene, which peaked after one hour. As expected, stimulation with BMP4/6 resulted in a significant increase in transcription of BMP target genes such as Smad7, Nog, Id1, Klf10, and Lif, but also a strong increase in transcription of Notch pathway genes such as Hes1, Lfng, and Hey1. We showed that the important BMP pathway effectors SMAD4 and pSMAD1/5/9 bind to the promoters of these Notch targets. Our results suggest that the rapid expression of genes encoding Notch signaling components is due to direct regulation by BMP signaling.
2023-10-01 | GSE127798 | GEO
Project description:We have established that BMP6 is an important endogenous regulator of human osteoblast differentiation. Our preliminary experiment showed that 8 hour BMP6 treatment induced early osteoblast markers in hMSC. In this study, we used microarrays to profile the global gene expression program in hMSC induced by BMP6 treatment and further identify the early osteogenic responses to BMP6 stimulation. Keywords: Stress response
2009-06-01 | GSE13604 | GEO
Project description:We have established that BMP6 is an important endogenous regulator of human osteoblast differentiation. Our preliminary experiment showed that 8 hour BMP6 treatment induced early osteoblast markers in hMSC. In this study, we used microarrays to profile the global gene expression program in hMSC induced by BMP6 treatment and further identify the early osteogenic responses to BMP6 stimulation. Experiment Overall Design: The dataset contains a total of 4 gene chip measurements from duplicate experiments each with paired measurements of human MSC with or without 8 hours BMP6 treatment.
2009-06-08 | E-GEOD-13604 | biostudies-arrayexpress
Project description:This experiment was carried out to identify the short-term effects of Activin A and BMP4 stimulation on gene expression in human embryonic stem cells grown in a chemically defined medium. Keywords: Growth factor stimulation experiment
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Project description:Growth suppressing Wnt/BMP4-Msx/Notch signalling in neuroblastoma
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Project description:Backround: Several microRNAs have been characterized to regulate the process of angiogenesis. Previously, bone morphogenetic protein 4 (BMP4) was shown to increase the proangiogenic activity of endothelial cells. Aim: In this project we investigated how the proangiogenic BMP4 effect is mediated by microRNAs. Experimental design: To investigate changes in the microRNA transcriptome in HUVECs a time course experiment (12, 18 and 24 h) was performed. HUVECs were kept in endothelial basal medium either with BMP4 (25 ng/ml) stimulation or buffer control (4 mM HCL with 0.1% bovine serum albumin). Comparison between stimulated vs. unstimulated cells at different time points. followed by a miRNA microarray analysis was performed.
2017-02-01 | E-MTAB-4383 | biostudies-arrayexpress
Project description:Molecular function of BMPs in metastatic melanoma progression is undefined. The goal of this study is to identify BMP6-activated gene signaturs associated with metastatic progresses in human cutaneous melanoma. Transcriptome profiles (RNA-seq) of three melanoma cell lines (WM1341D, WM983B, and 1205Lu) stably expressing BMP6 and coressponding control cells were generated by deep sequencing using illumona HiSeq and mapped more than 30 million sequencing reads per sample to the human genome (build Hg19). Gene signatures down-regulated by BMP6 are mostly associated with extracellular matrix organization and growth factor binding, suggesting a metastasis-suppressive role of BMP6 in melanoma.
2021-01-10 | GSE164495 | GEO
Project description:Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and often associated with increased levels of sEng. Although a pathogenic role for sEng involving hypertension has been reported in several animal models of preeclampsia, the exact molecular mechanisms implicated remain to be identified. To search for sEng-induced mediators, we have analyzed the protein secretome of human endothelial cells in the presence of sEng. We find that sEng induces the expression of BMP4 in endothelial cells, as evidenced by their proteomic signature, gene transcript levels and BMP4 promoter activity. A mouse model of preeclampsia with high sEng plasma levels (sEng+) showed increased levels of BMP4 transcripts in lungs and increased circulating BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appears 18 days after mating, precisely coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 are positively correlated in pregnant women with and without preeclampsia. Interestingly, sEng-induced arterial pressure elevation in sEng+ mice was abolished in the presence of the BMP4 inhibitor noggin, suggesting that BMP4 is a downstream mediator of sEng. These results provide a better understanding on the role of sEng in the pathobiology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.
2020-04-23 | PXD016228 | Pride