BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway [array]
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ABSTRACT:
PROVIDER: PRJNA525422 | ENA |
REPOSITORIES: ENA
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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:BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway
| PRJNA1310614 | ENA
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 | GSE159594 | GEO
Project description:BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway [RNA-seq I]
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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.
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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.
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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
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.
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