The effect of BMP4 and BMP6 stimulation on adult muscle stem cells (MuSC)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE159594 | GEO | 2023/10/01
REPOSITORIES: GEO
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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
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
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
Project description:BMP6 mediated osteoblast differentiation plays a key role in skeletal development and bone disease. Unfortunately, the signaling pathways regulated by BMP6 are largely uncharacterized due to both a lack of data and the complexity of the response. To better characterize the signaling pathways responsive to BMP6, we conducted a time series microarray study to track BMP6 induced osteoblast differentiation and mineralization. Human MSC cells underwent osteogenic induction with BMP6 treatment for 0 hours, 8 hours, 24 hours, and 96 hours, which correspond to four phenotypic groups, i.e. control, preosteoblast (no mineralization), (sub-maximal) mineralization, and maximal mineralization at 14 days after the initiation of BMP treatment (18 days in total). Cells were harvested at 8 hours, 24 hours, 96 hours and 10 days for microarray profiling. Assays were run in duplicate for a total of 26 arrays. We only used 20 arrays in the reference paper.
2011-09-19 | E-GEOD-28074 | biostudies-arrayexpress
Project description:Mutations in repulsive guidance molecule c (RGMc) / hemojuvelin (HJV) cause juvenile hemochromatosis, an aggravated iron overload disorder that presents early in life. Patients with juvenile hemochromatosis, and RGMc knockout mice, have diminished expression of the key iron-regulatory peptide, hepcidin. This suggests that RGMc plays a critical role in the regulation of iron homeostasis; however the mechanisms of RGMc actions are unknown. Recent studies have shown that RGMc directly binds to the growth factors, bone morphogenetic protein 2 and 6 (BMP2 and BMP6), and it is possible that this interaction regulates aspects of iron metabolism. We used microarrays to examine the effects of RGMc on BMP2- and BMP6-mediated gene expression. In our experimental model we treated Hep3B liver cells that had been serum starved for 16 hours as follows: (1) un-treated, (2) BMP2, (3) BMP2 + 10-fold molar excess of Noggin (a potent BMP2 inhibitor), (4) BMP2 + 20-fold molar excess of RGMc, (5) BMP6, (6) BMP6 + 10-fold molar excess of Noggin, (7) BMP6 + 20-fold molar excess of RGMc. Binding was allowed to proceed for BMP and Noggin or RGMc for 3 hr at 20°C prior to treatment of Hep3B cells. Treatment time was 4 hr at which cells were collected for RNA isolation.
2010-06-23 | E-GEOD-20671 | biostudies-arrayexpress
Project description:Background & Aims: Although hepcidin expression was shown to be induced by the BMP signaling pathway, it is not yet known how iron regulates hepcidin and which of the BMP molecules is the endogenous regulator of iron homeostasis in vivo. We therefore assessed liver transcription profiles of mice fed an iron-deficient or an iron-enriched diet and looked for genes that were regulated similarly to hepcidin in that context. Methods: Genome-wide liver expression profiles of mice of the B6 and D2 genetic backgrounds subjected to iron-deficient, -balanced, or -enriched diets were obtained using Agilent Whole Genome microarrays. Real-time quantitative-PCR and western-blots were used to confirm microarray results and compare gene expression variations induced by secondary iron deficiency or iron overload with those consecutive to Smad4 or Hamp1-deficiency. Results: Among 1419 transcripts significantly modulated by the dietary iron content, four were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, the regulator of Bmp/Smad signal transduction Smad7, the negative regulator of basic helix-loop-helix (bHLH) proteins Id1, and a protein with a bHLH domain, Atoh8. The iron overload developed by Smad4 and Hamp1-deficient mice also increased Bmp6 transcription. Body iron stores influence Smad1/5/8 phosphorylation and, as shown by analysis of mice with liver-specific disruption of Smad4, the binding partner for the receptor-activated Smads is necessary for activation of Smad7, Id1, and Atoh8 transcription by iron. Conclusions: Liver expression of Bmp6, Smad7, Id1, and Atoh8 is regulated by body iron stores and may participate in hepcidin regulation through the Bmp/Smad pathway. Keywords: response to dietary iron content
2008-07-07 | GSE10421 | GEO
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
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: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: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