MAGIC_18 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001210 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:By using ribosome profiling, we demonstrate that catalytic activity of the RNA helicase DDX3 is generally required for mediating translation repression under stress. Intriguingly, however, a cancer-related DDX3 variant DDX3 R534H selectively preserves translation of genes encoding core nucleosome components. Additionally, DDX3 variants also shift ORF usage on select genes, such as RPLP1 and stress-response factors as an added mechanism of translation regulation during stress. Thus, DDX3 through both extensive and selective interactions with RNA and the ribosomal machinery helps to remodel the translational landscape under stress and in cancer.
2016-04-21 | GSE70802 | GEO
Project description:We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse.
2015-04-23 | GSE62618 | GEO
Project description:Deregulation of N-myc is a leading cause of malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or on the analysis of the medulloblastoma transcriptome. Here, we have broadly characterized the translatome of medulloblastoma and shown that N-myc unexpectedly drives selective translation of transcripts that promote protein homeostasis. Cancer cells are constantly exposed to proteotoxic stress associated with alterations in protein production or folding. It remains poorly understood how cancers cope with proteotoxic stress to promote their growth. Here, our data unexpectedly revealed that N-myc regulates the expression of specific components (~5%) of the protein folding machinery at the translational level through the major cap binding protein, eukaryotic initiation factor eIF4E. Reducing eIF4E levels in mouse models of medulloblastoma blocked tumorigenesis. Importantly, targeting Hsp70, a protein folding chaperone translationally regulated by N-myc, suppressed tumor growth in mouse and human medulloblastoma xenograft models. These findings reveal a previously hidden molecular program that promotes medulloblastoma formation and identify new therapies that may have impact in the clinic.
2022-10-18 | GSE215298 | GEO
Project description:We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse. We investigated the DNA methylation profiles of 18 diagnostic and 22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray
2015-04-23 | E-GEOD-62618 | biostudies-arrayexpress
Project description:We report a novel resistance mechanism to CDK4/6 inhibition in Hedgehog-associated medulloblastoma where cell models and mouse models demonstrate that prolonged inhibition of CDK4/6 inhibits ribosome biogenesis, activates the unfolded protein response, and increases the amount of Smoothened-activating lipids. This RNA-Sequencing dataset represents genomically-engineered mouse medulloblastoma models that either have wild-type Cdk6 or genomic knockout of Cdk6. We find that tumors that grew despite genetic loss of Cdk6 have suppresed ribosome biogenesis.
2021-01-06 | GSE164311 | GEO
Project description:Stress-related psychiatric disorders and the stress system show prominent differences between men and women. These sex differences are detectable at the transcriptional level but we lack cell-type specific information. Here, using single-cell transcriptomics, we identify cell-type-specific signatures of acute restraint stress in the paraventricular nucleus of the hypothalamus - a central hub of the stress response - in male and female mice. Further, we show that a history of chronic mild stress alters these acute stress signatures in a sex-specific way. Using this dataset, we identified oligodendrocytes as a major target for sex-specific effects of stress. This dataset provides the first molecular resource for an in-depth dissection of the interplay between cell types and sex on the mechanisms of the stress response, offering the transcriptomes of thousands of individual cells.
2023-07-31 | GSE201032 | GEO
Project description:In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. To identify proteins with an altered synthesis pattern in response to mupirocin treatment we used the highly sensitive 2-dimensional gel electrophoresis technique in combination with mass spectrometry. Obtained results were complemented by DNA-microarray, Northern blot and metabolome analysis. Whereas expression of genes involved in nucleotide biosynthesis, DNA metabolism, energy metabolism and translation was significantly down-regulated, expression of the isoleucyl-tRNA synthetase, the branched chain amino acids pathway, genes with functions in oxidative stress resistance (ahpC, katA), putative roles in stress protection (SACOL1759, SACOL2131, SACOL0815) and transport processes was increased. Of particular interest were the differences in the transcription of genes encoding virulence associated regulators (i.e. arlRS, saeRS, sarA, sarR, sarS) as well as genes directly involved in the virulence of S. aureus (i.e. fnbA, epiE, epiG, seb). In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. In total four independent hybridization experiments with each representing a biological replicate including a control and a treated sample were carried out. To account for the dye bias two of the four replicates were dye swapped.
2012-01-23 | E-GEOD-30743 | biostudies-arrayexpress
Project description:Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multi-vesicular body (MVB) pathway. Combined loss of vacuolar amino acid storage, MVBs and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homoeostasis through post-translational nutrient transporter remodeling.
2021-07-22 | ST001901 | MetabolomicsWorkbench
Project description:Integrated Stress Response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. With acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by translation normalization. Here, we report a dramatically different response during more physiologically relevant chronic ER stress. This unique ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. PERK-dependent switching from eIF4F/eIF2B- to eIF3D/GADD34-regulated translation initiation results in partial but not complete translation recovery, and together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of these transcriptional and translational changes prevents ER dysfunction and inhibits “foamy cell” development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.
2018-01-05 | GSE90070 | GEO
Project description:Fluid shear stress response in medulloblastoma cell lines
| PRJNA927002 | ENA