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GSE73042
Homo sapiens
14 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunoglobulin light-chain amyloidosis (AL) is a rare clonal plasma cell (PC) disorder that remains largely incurable. AL and multiple myeloma (MM) share the same cellular origin, but while knowledge about MM PC biology has improved significantly, the same does not apply for AL. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 22 newly-diagnosed AL patients. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and MGUS or MM patients. However, in contrast to MM, highly-purified FACSs-sorted clonal PCs in AL (n=9/22) show virtually normal transcriptomes with only 68 deregulated genes as compared to normal PCs, including a few tumor suppressor (CDH1, RCAN) and pro-apoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11/22) were genomically unstable with a median of 9 copy-number-abnormities (CNAs) per case; many of which similar to those found in MM. Whole-exome sequencing (WES) was performed in three AL patients and revealed a median of 10 non-recurrent mutations per case. Altogether, we showed that although clonal PCs in AL display phenotypic and CNA profiles similar to MM, their transcriptome is remarkably similar to that of normal PCs. First-ever WES revealed the lack of a unifying mutation in AL
Publication Title
Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD8+ T cells and NK cells protect from viral infections by killing virally-infected cells and secreting interferon-g. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses.
Publication Title
The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8⁺ T Cells in Response to a Lethal Poxvirus Infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Analysis of L-Myc-dependent genes in pDCs and classical DC subsets with and without stimulation.
Publication Title
L-Myc expression by dendritic cells is required for optimal T-cell priming.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
DNMT3A mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Here we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Dnmt3a ablation led to a lethal, fully penetrant myeloproliferative neoplasm with myelodysplasia (MDS/MPN) characterized by marked, progressive hepatomegaly that was transplantable. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo. Overall design: Dnmt3af/f mice (Nguyen et al) were crossed into hematopoietic-specific inducible Mx1-Cre deletor line; we examined transcriptomes from FACS-sorted LSK and GMP populations from Dnmt3af/f Mx1-Cre+ (KO) and Dnmt3af/f Mx1-Cre- (CTRL) animals at 12 months of age
Publication Title
Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Cancer cells alter their metabolism to support their malignant properties. By transcriptomic analysis we identified the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) as strongly correlated with epithelial-to-mesenchymal transition (EMT). This association was confirmed staining samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing profiling confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGF-Beta signature genes. Mechanistically, excess glucose was found to promote EMT through autocrine TGF-Beta stimulation, while PP-deficient cells were refractory to glucose-induced EMT. PP represents a molecular link between glucose metabolism and cancer differentiation and aggressiveness, and a novel potential therapeutic target. Overall design: 3x3 biological replicated samples; 2 groups of samples with shRNA-mediated specific gene inhibition and scrambled control cells
Publication Title
Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray expression profiling has become a valuable tool in the evaluation of the genetic consequences of metabolic disease. Although 3-biased gene expression microarray platforms were the first generation to have widespread availability, newer platforms are gradually emerging that have more up-to-date content and/or higher cost efficiency. Deciphering the relative strengths and weaknesses of these various platforms for metabolic pathway level analyses can be daunting. We sought to determine the practical strengths and weaknesses of four leading commercially-available expression array platforms relative to biologic investigations, as well as assess the feasibility of cross-platform data integration for purposes of biochemical pathway analyses. METHODS: Liver RNA from B6.Alb/cre,Pdss2loxP/loxP mice having primary Coenzyme Q deficiency was extracted either at baseline or following treatment with an antioxidant/antihyperlipidemic agent, probucol. Target RNA samples were prepared and hybridized to Affymetrix 430 2.0, Affymetrix Gene 1.0 ST, Affymetrix Exon 1.0 ST, and Illumina Mouse WG-6 expression arrays. Probes on all platforms were re-mapped to coding sequences in the current version of the mouse genome. Data processing and statistical analysis were performed by R/Bioconductor functions, and pathway analyses were carried out by KEGG Atlas and GSEA. RESULTS: Expression measurements were generally consistent across platforms. However, intensive probe-level comparison suggested that differences in probe locations were a major source of inter-platform variance. In addition, genes expressed at low or intermediate levels had lower inter-platform reproducibility than highly expressed genes. All platforms showed similar patterns of differential expression between sample groups, with steroid biosynthesis consistently identified as the most down-regulated metabolic pathway by probucol treatment. CONCLUSIONS: This work offers a timely guide for metabolic disease investigators to enable informed end-user decisions regarding choice of expression microarray platform best-suited to specific research project goals. Successful cross-platform integration of biochemical pathway expression data is also demonstrated, especially for well-annotated and highly-expressed genes. However, integration of gene-level expression data is limited by individual platform probe design and the expression level of target genes. Cross-platform analyses of biochemical pathway data will require additional data processing and novel computational bioinformatics tools to address unique statistical challenges.
Publication Title
Cross-platform expression microarray performance in a mouse model of mitochondrial disease therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Sirtuins (Sirt) are a family of enzymes that modify chromatin and other proteins to affect gene activity. Loss of Sirt6 leads to a progeria-like phenotype in mice, but the target of SIRT6 action has been elusive. Here we show that Sirt6 binds to thousands of gene promoters in a stress-inducible fashion, guided by the stress-responsive transcription factor NF-B.
Publication Title
Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Danio rerio
- 47 Downloadable Samples
- IlluminaHiSeq2500
Description
We have discovered subsets of axon guidance molecules and transcription factors that are enriched in specific subsets of olfactory sensory neurons. We have demonstrated guidance activity for three of the candidate axon guidance genes we identified, suggesting that this approach is an efficient method for characterizing guidance systems relevant to olfactory axon targeting. Overall design: Single-cell RNASeq of OMP-expressing olfactory sensory neurons was performed by capture on Fluidigm-C1 followed by sequencing on Illumina HiSeq2500
Publication Title
Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons.
Sample Metadata Fields
No sample metadata fields
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