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SRP097847
Mus musculus
24 Downloadable Samples
Illumina HiSeq 4000
Description
Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. Overall design: RNA-sequencing of 12 Smarcb1-deficient mouse cranial nerves and meninges tumors
Publication Title
Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
Publication Title
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A prominent enzyme in organellar RNA metabolism is the exoribonuclease polynucleotide phosphorylase (PNPase), whose reversible activity is governed by the nucleotides diphosphate-inorganic phosphate ratio. In Chlamydomonas reinhardtii, PNPase regulates chloroplast transcript accumulation in response to phosphorus (P) starvation, and PNPase expression is repressed by the response regulator PSR1 under these conditions. Here, we investigated the role of PNPase in the Arabidopsis (Arabidopsis thaliana) P deprivation response by comparing wild-type and pnp mutant plants with respect to their morphology, metabolite profiles, and transcriptomes. We found that P-deprived pnp mutants develop aborted clusters of lateral roots, which are characterized by decreased auxin responsiveness and cell division, and exhibit cell death at the root tips. Electron microscopy revealed that the collapse of root organelles is enhanced in the pnp mutant under P deprivation and occurred with low frequency under P-replete conditions. Global analyses of metabolites and transcripts were carried out to understand the molecular bases of these altered P deprivation responses. We found that the pnp mutant expresses some elements of the deprivation response even when grown on a full nutrient medium, including altered transcript accumulation, although its total and inorganic P contents are not reduced. The pnp mutation also confers P status-independent responses, including but not limited to stress responses. Taken together, our data support the hypothesis that the activity of the chloroplast PNPase is involved in plant acclimation to P availability and that it may help maintain an appropriate balance of P metabolites even under normal growth conditions.
Publication Title
Abnormal physiological and molecular mutant phenotypes link chloroplast polynucleotide phosphorylase to the phosphorus deprivation response in Arabidopsis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primary brain tumors are classified and treated based on their histological features, however the factors which specify these tumor types remain largely unknown. We demonstrate that the over-expression of HRAS (V12) and MYC alone or in combination directs the development of glioma, CNS PNET, and atypical teratoid/rhabdoid (AT/RT)-like tumors from postnatal murine p53-deficient neural stem/progenitor cells.
Publication Title
Definition of genetic events directing the development of distinct types of brain tumors from postnatal neural stem/progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. Overall design: The experiments were performed in quadruplicates for each condition with a total of 12 samples
Publication Title
Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.
Publication Title
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
let-7c and miR-294 were transfected into Dgcr8 -/- miRNA deficient ES cells and RNA was harvested after 12 hours
Publication Title
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dicer, which is required for the processing of both microRNAs (miRNAs) and small interfering RNAs (siRNAs), is essential for oocyte maturation. Oocytes express both miRNAs and endogenous siRNAs (endo-siRNAs). To determine whether the abnormalities in Dicer knockout oocytes during meiotic maturation are secondary to the loss of endo-siRNAs and/or miRNAs, we deleted Dgcr8, which encodes a RNA binding protein specifically required for miRNA processing. In striking contrast to Dicer, Dgcr8 deficient oocytes matured normally and, when fertilized with wild-type sperm, produced healthy appearing offspring, even though miRNA levels were reduced to similar levels as Dicer deficient oocytes. Furthermore, the deletion of both maternal and zygotic Dgcr8 alleles did not impair preimplantation development including the determination of the inner cell mass (ICM) and trophectoderm. Most surprisingly, the mRNA profiles of wild-type and Dgcr8 null oocytes were essentially identical while Dicer null oocytes showed hundreds of misregulated transcripts. These findings show that miRNA function is globally suppressed during oocyte maturation and preimplantation development and that endo-siRNAs, rather than miRNAs, underlie the Dicer knockout phenotype in oocytes.
Publication Title
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Forkhead BoxO (FoxO) transcription factors expressed in adult skeletal muscle promote muscle atrophy during various catabolic conditions. We have identified the genome wide target genes and biological networks regulated by FoxO in skeletal muscle during Colon-26 (C-26) cancer cachexia.
Publication Title
Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples