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SRP173282
Homo sapiens
15 Downloadable Samples
Illumina HiSeq 2500
Description
MM.1S orthotopic tumors were analyzed fro their gene expression upon tumor outgrowth. In contorl/bortezomib/elesclmol and combo treatments. Overall design: examination of three tumors for each condition.
Publication Title
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We transiently induce the Lo19S state with a dox inducible shRNa targeting PSMD2 and explore the gene expression in the presence and absence of bortezomib Overall design: one cell type (T47D), two states (Control and Lo19S) with and without treatment with 20nM bortezomib , all in triplicates
Publication Title
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq 500
Description
Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer. Overall design: RNA-seq in TTC642 MRT cells treated with idasanutlin compared to DMSO
Publication Title
MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells (strain L) and cultured.
Publication Title
Genetic and transcriptional evolution alters cancer cell line drug response.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
Mre11, together with Rad50 and Xrs2/NBS, plays pivotal roles in homologous recombination, repair of DNA double strand breaks (DSBs), activation of damage-induced checkpoint, and telomere maintenance. Using DNA microarray assays to analyze yeast mutants (mre11delta, rad50delta, and spo11Y135F) defective for meiotic DSB formation, we demonstrate that the absence of Mre11 in yeast causes specific effects on regulation of a class of meiotic genes for spore development. The transcriptional deficiency was not observed in other DSB mutants such as rad50delta and spo11Y135F, suggesting the transcriptional defect in mre11delta is due to neither lack of meiotic DSB formation, nor disintegrity of Mre11-Rad50-Xrs2 complex.These defects were confirmed by northern and lacZ reporter gene assays.
Publication Title
Mre11 mediates gene regulation in yeast spore development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We demonstrated that, four weeks after the pulmonary artery banding (PAB) operation, rats could be divided into two groups: an F+ group in which the fibrotic area occupied more than 6.5% of the whole area of the heart tissues, and an F- group in which the fibrotic area occupied less than 6.5% of this area.
Publication Title
Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Schizosaccharomyces pombe
- 4 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Schizosaccharomyces pombe
- 4 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Meiotic homologous recombination is a critical DNA-templated event for sexually-reproducing organisms. It is initiated by a programmed formation of DNA double strand breaks (DSBs), mainly formed at recombination hotspots, and is, like all other DNA-related processes, under great influence of chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. In addition, DSB is proposed to occur in a higher-order chromatin architecture termed axis-loop, in which many loops protrude from proteinaceous axis. Despite many recent insightful studies, still much remains unknown about how meiotic DSBs are generated in chromatin structure. Here, we show that the highly conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Subsequent investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained in the absence of H2A.Z. Instead, we found that H2A.Z facilitates chromatin binding of various proteins required for DSB formation. Strikingly, artificial tethering of one of such proteins, Rec10, to chromatin partially restored DSB reduction in H2A.Z-lacking cells. Based on these, we conclude that fission yeast H2A.Z promotes initiation of meiotic recombination partly through delivering DSB-related proteins onto chromatin.
Publication Title
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The fields of drug discovery and regenerative medicine require large numbers of adult human primary hepatocytes. For this purpose, it is desirable to use hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells. To develop an efficient HLCs induction method, we constructed a red fluorescent reporter, CYP3A7R, in which DsRed is placed under the transcriptional regulation of CYP3A7 coding for a human fetus-type P450 enzyme. We created transgenic mice using mouse embryonic stem cells (mESCs) carrying a CYP3A7R transgene.
Publication Title
Real-time fluorometric evaluation of hepatoblast proliferation in vivo and in vitro using the expression of CYP3A7 coding for human fetus-specific P450.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 31 Downloadable Samples
- Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
Brassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Publication Title
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples