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GSE51925
Mus musculus
33 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Old C57BL/6 mice cannot mount an effective innate immune response
Publication Title
Aged mice are unable to mount an effective myeloid response to sepsis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of primary human umbilical vein endothelial cells (HUVEC) infected by piliated and adherent wild-type (WT), frpC/frpA-deficient mutant, or the non-adherent (pilD) N. meningitidis MC58 bacteria defective in production of the type IV pilus, respectively. Surprisingly, no significant difference was found between the transcriptomes of HUVECs infected by bacteria producing, or not the RTX FrpC and FrpA proteins, thus failing to provide any hints on their biological activity. In contrast, pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response or adhesion. In particular, genes for signaling pathway proteins involved in early embryonic development, such as transforming growth factor- (TGF-)/Smad, Wnt/-catenin, and Notch/Jagged were found to be upregulated upon adhesion of N. meningitidis together with genes for a number of transcription factors. This reveals that adhering piliated meningocci manipulate signaling pathways controlling human cell proliferation, survival and defense mechanisms, while establishing a commensal relationship with the host.
Publication Title
Meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The tumor suppressor TP53 is mutated in the majority of human cancers, including over 70% of pancreatic ductal adenocarcinoma (PDAC). Wild-type p53 accumulates in response to cellular stress and regulates the expression of genes that alter cell fate and constrain tumorigenesis. p53 also modulates several cellular metabolic pathways, though it remains unclear whether particular p53-regulated metabolites contribute to tumor suppression or whether metabolic alterations driven by p53 mutation sustain cancer progression. Here, we show that restoring endogenous p53 function in cancer cells derived from a murine PDAC model driven by oncogenic Kras and a regulatable p53 short hairpin RNA (shRNA) rewires glucose and glutamine metabolism leading to the accumulation of a-ketoglutarate (aKG), an obligate substrate for several chromatin modifying enzymes. p53 induces transcriptional programs characteristic of premalignant differentiation, an effect that can be partially recapitulated by addition of cell permeable aKG. Similarly, enforcing aKG accumulation in p53-deficient PDAC cells though the inhibition of oxoglutarate (aKG) dehydrogenase (Ogdh), the enzyme that consumes aKG in the tricarboxylic acid cycle, reduces tumor-initiating capacity and promotes tumor cell differentiation. Decreases in 5-hydroxymethylcytosine (5hmC), an aKG-dependent chromatin modification, are associated with the appearance of p53 mutations in the transition from premalignant to de-differentiated malignant lesions, whereas increases in 5hmC accompany tumor cell differentiation triggered by either p53 restoration or Ogdh depletion. Together these data nominate aKG as an effector of p53-mediated tumor suppression whose accumulation in p53-deficient tumors can drive tumor cell differentiation and antagonize malignant progression. Overall design: 6 samples were analyzed in duplicates of 3 conditions. 1. Control, KPsh cells grown on dox, treated with vehicle DMSO for 72 hours. 2. KPsh cells grown on dox, treated with 4mM cell permeable dimethyl-alpha ketoglutarate for 72 hours. 3. KPsh cells grown off dox for 8 days, treated with DMSO vehicle for 72 hours.
Publication Title
α-Ketoglutarate links p53 to cell fate during tumour suppression.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 95 Downloadable Samples
- IlluminaHiSeq2500
Description
The purpose of current study is to identify the differentiated gene expression associated with mouse 11B3 deletion, syntenic to human chromosome 17p13.1. We compared four different mouse acute myeloid leukemia cells, freshly isolated from mouse bone marrows with either 11B3fl/p53fl;shNf1;shMll3;Vav1-Cre or p53fl/fl;shNf1;shMll3;Vav1-Cre. The RNA-seq results indicate that genes located on chromosome 11B3 mostly reduce gene expression level in 11B3 deleted leukemia cells. Overall design: Examination RNA expression level in 11B3-deleted vs p53-loss only samples.
Publication Title
Deletions linked to TP53 loss drive cancer through p53-independent mechanisms.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Using RNA-seq we identified the gene expression changes in GC B cells from LSD1 wild-type or LSD1-deficient mice immunized with T cell dependent antigens (Sheep Red Blood cells) Overall design: RNA seq of sorted GC B cell populations from 3 littermate mice per genotype (3 wild-type, 3 knockout)
Publication Title
Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 28 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Muscles organise a pseudo-crystalline array of actin, myosin and titin filaments to build force-producing sarcomeres. To study how sarcomeres are built, we performed mRNA-sequencing of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, two clusters are strongly enriched for sarcomeric components. Temporal gene expression together with detailed morphological analysis enabled us to define two distinct phases of sarcomere development, both of which require the transcriptional regulator Spalt major. During the first sarcomere formation phase, 2.0 µm long immature sarcomeres assemble myofibrils that spontaneously contract. In the second sarcomere maturation phase, sarcomeres grow to their final 3.2 µm length and 1.5 µm diameter and acquire stretch-sensitivity. Interestingly, the final number of myofibrils per flight muscle fiber is determined at the onset of the first phase and remains constant. Together, this defines a biphasic mode of sarcomere and myofibril morphogenesis – a new concept which may also apply to vertebrate muscle or heart development. Overall design: Part I: An 8-point timecourse of wild-type flight muscle development in Drosophila melanogaster was analyzed with duplicates/triplicates for each timepoint Part II: A Mef2-Gal4 x salmIR timecourse in duplicate at 4 timepoints was compared to wild-type flight muscle
Publication Title
A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background:
Publication Title
Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate the impact of ablating Bcl9/Bcl9l on tumorigenesis, 6-8- week-old mice were exposed first to a single dose dimethylhydrazine (DMH, 44 mg/kg body weight), which is metabolized in the liver to carcinogenic azoxymethane (AOM), followed by 7 days oral administration of 2 % dextrane sulfate sodium (DSS) in the drinking water. This regimen results in the emergence of dysplastic adenomas, which progress to differentiated adenocarcinomas that are morphologically similar to human colorectal adenocarcinomas and typically harbor -catenin stabilizing mutations of GSK3 phosphorylation sites. Accordingly, these tumors present hallmarks of active Wnt signaling such as accumulation of nuclear -catenin and expression of Wnt target genes.
Publication Title
Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Canonical Wnt signaling output is mediated by ß-catenin, which interacts with LEF/TCF transcription factors and recruits a general transcriptional activation complex to its C-terminus. Its N-terminus binds BCL9/9L proteins, which bind co-activators that in mammals contribute to fine-tuning the transcriptional output. We found that a BCL9/9L-dependent gene expression signature was strongly associated with patient outcome in colorectal cancer and that stem cell and mesenchymal genes determine its prognostic value. Abrogating BCL9/9L-ß-catenin signaling in independent mouse colorectal cancer models resulted in virtual loss of these traits, and oncogenic intestinal organoids lacking BCL9/9L proteins proved no longer tumorigenic. Our findings suggest that the BCL9/9L arm of Wnt-ß-catenin signaling sustains a stemness-to-differentiation equilibrium in colorectal cancer, which critically affects disease outcome. Mutational activation of the Wnt pathway is a key oncogenic event in colorectal cancer. Targeting the pathway downstream of activating mutations is challenging, and the therapeutic window is limited by intestinal toxicity. Contrasting with phenotypes caused by inactivating key Wnt pathway components, ablation of BCL9/9L proteins in adult mice indicated that they were dispensable for intestinal homeostasis, consistent with their role in tuning transcription. Cancer stem cells are increasingly recognized as responsible for tumor recurrence. The correlation between stemness traits in colorectal cancer models and BCL9/9L-ß-catenin signaling suggests that high Wnt signaling output is required for their maintenance. Our findings suggest that pruning Wnt-ß-catenin signaling might be well tolerated and prove sufficient for trimming stemness traits and improving disease outcome. Overall design: Examination of Bcl9/9l-knockout versus wild-type transcriptome in murine AOM-DSS tumors, APC-Kras tumors and healthy colocyte extracts.
Publication Title
BCL9/9L-β-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the pediatric, elderly, and immune compromised populations. A gap in our understanding of hRSVdisease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralog of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 WT or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I IFN responses, suppression of dendritic cell maturation, and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV associated morbidity and mortality. Overall design: 12 samples where analysed. A549 cell line was infected with mock, hRSV or mutated hRSV virus. Samples are: control mock-infected (2 replicas), hRSV wild-type NS1 infected (3 replicas), hRSV NS1 1-118 infected (3 replicas), hRSV NS1 L132A/L133A infected (2 replicas) and hRSV NS1 Y125A infected (2 replicas). Libraries was prepared for 96 h.p.i.
Publication Title
Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses.
Sample Metadata Fields
Cell line, Subject
View Samples