Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid [RNA-seq]
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PROVIDER: PRJNA1067126 | ENA |
REPOSITORIES: ENA
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Project description:Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid [ChIP-seq]
| PRJNA1067130 | ENA
Project description:Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to act primarily via differentiation. However, this has never been conclusively demonstrated in vivo. Curiously, RA has little effect shrinking primary human tumors when applied in upfront treatment but can eliminate neuroblastoma cells from the bone marrow during consolidation therapy—a discrepancy that has never been explained. To investigate this, we treated a large cohort of neuroblastoma cell lines with RA and observed that the most RA-sensitive cells tended to undergo apoptosis or senescence, rather than differentiation. We conducted genome-wide CRISPR knockout screens under RA treatment, which identified BMP signaling as controlling the apoptosis/senescence vs differentiation cell fate decision and RA’s overall potency. We then conducted integrative analysis of high throughput ChIP-seq and RNA-seq data, which indicates that downstream BMP and RA transcription factors cooperate to determine cell fate, following exposure to RA.
2024-05-31 | GSE253785 | GEO
Project description:Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to act primarily via differentiation. However, this has never been conclusively demonstrated in vivo. Curiously, RA has little effect shrinking primary human tumors when applied in upfront treatment but can eliminate neuroblastoma cells from the bone marrow during consolidation therapy—a discrepancy that has never been explained. To investigate this, we treated a large cohort of neuroblastoma cell lines with RA and observed that the most RA-sensitive cells tended to undergo apoptosis or senescence, rather than differentiation. We conducted genome-wide CRISPR knockout screens under RA treatment, which identified BMP signaling as controlling the apoptosis/senescence vs differentiation cell fate decision and RA’s overall potency. We then conducted integrative analysis of high throughput ChIP-seq and RNA-seq data, which indicates that downstream BMP and RA transcription factors cooperate to determine cell fate, following exposure to RA.
2024-05-31 | GSE253786 | GEO
Project description:The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by the entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence–most typically, DNA demethylation of relevant genes–which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Ou findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.
2017-09-12 | GSE94136 | GEO
Project description:Melanoma is a highly aggressive skin cancer, which has the fastest and second fastest growing incidence of any cancer in men and women, respectively. Although melanoma accounts for 5% of skin cancers, it is responsible for 80% of deaths related to skin cancers. The lifetime risk of melanoma is currently estimated to be 1 in 75 and is rising every year. The present study shows that inhibition of bone morphogenetic protein (BMP) signaling pathway is a potential target for treating metastatic melanoma. To characterize the underlying signaling mechanism, comparative proteomic profile of the mouse melanoma tissue treated with and BMP inhibitor (LDN193189) with untreated controls was performed using liquid chromatography-tandem mass spectrometry. Our mass spectrometry data analysis leads to identification of a total of 3231 nonredundant proteins. Of the 3231 proteins, 117 were up-regulated (fold change≥ 1.5) while 14 were down-regulated (fold change ≤ 0.66). Pathway enrichment analysis showed that altered proteins were primarily grouped into: regulation of actin cytoskeleton, phagosomes, proteoglycans in cancer, Focal adhesion, ECM receptor interaction and fatty acid metabolism pathway. Our studies suggest that inhibition of the BMP signaling cascade with small molecule inhibitors decreased the expression of the MT1 and MT2 (metallothionine 1 and 2) which are well known for the antiapoptotic, antioxidant, proliferative, and angiogenic effects in cancer.
2022-02-15 | PXD016088 | Pride
Project description:We report the systematic identification of BMP (bone morphogenetic protein) target genes in zebrafish during dorsal-ventral patterning using RNA-sequencing.
2020-07-30 | GSE135100 | GEO
Project description:Optogenetics is a rapidly advancing technology that combines photochemical, optical and synthetic biology techniques to control cellular behaviour and physiology. Combining sensitive light responsive optogenetic intervention tools with human pluripotent stem cell differentiation models has the potential to refine differentiation and unpick the processes by which morphogenetic signals direct tissue patterning, organisation and cell specification. Here, we utilised an optogenetic bone morphogenetic protein (BMP) signalling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs). We initially engineered light-sensitive hESCs through CRISPR/Cas9-mediated integration of the optoBMP system into the AAVS1 locus. Activation of optoBMP with blue light in lieu of BMP family growth factors during differentiation resulted in activation of BMP signalling pathway mechanisms and upregulation of a chondrogenic phenotype, with significant transcriptional differences compared to cells left in the dark. Furthermore, cells differentiated with light were capable of forming chondrogenic pellets consisting of a hyaline-like cartilaginous matrix.
2023-11-09 | E-MTAB-13377 | biostudies-arrayexpress
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
Project description:Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by a decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from diabetic individuals and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1 and Hey-1, transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism of BMP-2 induced beta cell dysfunction and identity loss. Mouse islets exposed to BMP-2 for 10 days showed impaired insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of beta cell specific identity and proliferation markers such as Ins1, Ucn3 and Ki67 but increased expression of Id1-4, Hes-1 and Hey-1. BMP-2 regulated mRNA expression significantly correlated with corresponding protein expression. BMP-2 induced gene expression changes were associated with a predominant reduction in the H3K27ac mark and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2-induced beta cell dysfunction is associated with epigenetic changes, predominantly a reduction in H3K27ac and a decrease in NeuroD1 DNA binding resulting in altered beta cell gene expression.
2023-07-20 | PXD036655 | Pride
Project description:Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.
| PRJEB64544 | ENA