Filters
Technology
Platform
GSE65384
Mus musculus
26 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Illumina HiSeq 2000
Description
To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulators Zeb1 and Tcf4 significantly reduced leukemic blast invasion. By classifying mouse and human leukemia according to Evi1/EVI1and Erg/ERG expression, reflecting aggressiveness and cell-of-origin and performing comparative transcriptomics we identified numerous EMT-related genes that were significantly associated with poor overall survival of AML patients. Overall design: RNA from FACS sorted bone marrow subpopulations was isolated, RNA-sequencing libraries were prepared and sequenced on an Illumina HiSeq 2000. Reads mapping to RefSeq transcripts were counted.
Publication Title
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulators Zeb1 and Tcf4 significantly reduced leukemic blast invasion. By classifying mouse and human leukemia according to Evi1/EVI1and Erg/ERG expression, reflecting aggressiveness and cell-of-origin and performing comparative transcriptomics we identified numerous EMT-related genes that were significantly associated with poor overall survival of AML patients.
Publication Title
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 359 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Transcriptional profiles are increasingly used to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood RNA signatures and local and systemic immune mediator levels in a large cohort of adults hospitalised with influenza from which extensive clinical and investigational data was obtained. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation, an inflammatory, activated neutrophil and cell stress/death (bacterial) pattern was seen, even early after disease onset. Identifiable bacterial co-infection was not necessary for this bacterial signature but could enhance its development while attenuating the early viral signature. Our findings emphasise the importance of timing and severity in the interpretation of transcriptomic profiles and soluble mediator levels, and identify specific patterns of immune activation that may enable the development of novel diagnostics and therapeutics
Publication Title
Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.
Sample Metadata Fields
Sex, Age, Race, Subject, Time
View Samples- Mus musculus
- 94 Downloadable Samples
- Illumina HiSeq 4000
Description
We have performed modular analyses to decipher the global transcriptional response and capture a breadth of distinct immune responses in the lungs and blood of mice infected or challenged with a broad spectrum of infectious pathogens, including parasites (Toxoplasma gondii), bacteria (Burkholderia pseudomallei), viruses (Influenza A virus and Respiratory Syncytial virus (RSV)) and fungi (Candida albicans), or allergens (House dust mite (HDM), systemic and intra-nasal challenge). In a distinct set of infectious diseases, we tested the blood modular transcriptional signatures in mice infected with Plasmodium chabaudi chabaudi (malaria), murine cytomegalovirus (MCMV), Listeria monocytogenes and chronic Burkholderia pseudomallei. We also investigated the transcriptional profiles of sorted CD4 T cells (total CD4+, CD4+ CD44 high and CD4+ CD44 low) from lung and blood samples from mice challenged with HDM allergen. Moreover, we used mice deficient in either Ifnar or Ifngr, or both, to reveal the individual roles of each pathway in controlling disease in mice infected with Toxoplasma gondii. Overall design: RNA-seq analysis of blood samples obtained from mice infected with Plasmodium chabaudi chabaudi, murine cytomegalovirus (MCMV), Listeria monocytogenes and chronic Burkholderia pseudomallei.
Publication Title
Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 4000
Description
We have performed modular analyses to decipher the global transcriptional response and capture a breadth of distinct immune responses in the lungs and blood of mice infected or challenged with a broad spectrum of infectious pathogens, including parasites (Toxoplasma gondii), bacteria (Burkholderia pseudomallei), viruses (Influenza A virus and Respiratory Syncytial virus (RSV)) and fungi (Candida albicans), or allergens (House dust mite (HDM), systemic and intra-nasal challenge). In a distinct set of infectious diseases, we tested the blood modular transcriptional signatures in mice infected with Plasmodium chabaudi chabaudi (malaria), murine cytomegalovirus (MCMV), Listeria monocytogenes and chronic Burkholderia pseudomallei. We also investigated the transcriptional profiles of sorted CD4 T cells (total CD4+, CD4+ CD44 high and CD4+ CD44 low) from lung and blood samples from mice challenged with HDM allergen. Moreover, we used mice deficient in either Ifnar or Ifngr, or both, to reveal the individual roles of each pathway in controlling disease in mice infected with Toxoplasma gondii. Overall design: RNA-seq analysis of sorted CD4 T cells (total CD4+, CD4+CD44high and CD4+CD44low) from lung and blood samples obtained from mice challenged systemically with House dust mite (HDM) allergy.
Publication Title
Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 14 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated.
Publication Title
Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4 mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS.
Publication Title
Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 525 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. 28 CEBPAdouble-mut and 13 CEBPAsingle-mut cases. CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1 mutation, white blood cell count and age. In contrast, CEBPAsingle-mut AMLs did not express a discriminating signature and could not be distinguished from wild type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance.
Publication Title
Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 537 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pretreatment karyotype of leukemic blasts is currently the key determinant in therapy decision-making in acute myeloid leukemia (AML). However, approximately fifty percent of AML patients, often carrying a normal karyotype, are currently unclassifiable based these established methods. Gene expression profiling has proven to be valuable for risk stratification of AML.
Publication Title
Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples