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Homo sapiens
155 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. A 40-gene CHEK2 signature was defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.
Publication Title
Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background and aim: The Insulin-like growth factor (IGF) axis is increasingly suggested to be involved in fatty liver disease and progression. We identified IGFBP2 as transcriptional regulatory effect network in liver steatosis and conducted a translational approach of its role in liver pathology from mouse to human, and whether it is influenced by conventional clinical intervention that mitigate hepatic steatosis. Methods: Primary hepatocytes from either C57Bl6 controls, alb-SREBP-1c mice with moderate transgene induced hepatic lipid accumulation or aP2-SREBP-1c mice with massive ectopic hepatic lipid accumulation, were analyzed to identify regulatory networks based on differentially regulated hepatic gene expression. In a translational approach, serum of morbidly obese patients with and without diabetes and biopsy-proven NAFLD were used for ELISA-based validation of mouse data. Moreover, sera of patients undergoing intervention were analyzed and correlated to liver fat content. Results: Comparative knowledge-based transcriptome analysis identified IGFBP2 as top score regulatory effect network between moderate and aggravated fatty liver in mouse models. The reduced expression of IGFBP2 in aP2-SREPB-1c progressed fatty liver associated with Igfbp2 promoter hypermethylation. Reduced secretion of IGFBP2 from aP2-SREBP-1c hepatocytes was reflected in the circulation of the animals. In this phenotype, reductions of IGFBP2 were accompanied by reduced fatty acid oxidation and increased methyltransferase and SIRT activity. Physiologically, IGFBP2 has no direct impact on lipid metabolism but might modulate IGF1 action on de novo lipogenesis. In humans, IGFBP2 levels declined from non-obese men to morbidly obese men with NAFLD and NASH. In intervention study reductions in liver fat correlated with restoration of IGFBP2 serum levels to values found in healthy individuals in morbidly obese patients following bariatric surgery. Conclusion: In hepatic metabolism changes of IGFBP2 abundance is connected to lipid metabolism whereas changes in IGFBP2 secretion were directly reflected in the circulation. IGFBP2 serum concentration correlates with the degree of fatty liver, which seems to be related to plasticity of the adipose tissue. These data provide IGFBP2 as a potential non-invasive biomarker for fatty liver disease directly reflecting the degree of impaired liver function with the potential to indicate progressed fatty liver disease.
Publication Title
Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.
Sample Metadata Fields
Sex, Age
View Samples
SRP065507- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
SynapTRAP. Identification of Synaptic mRNA of neurons of the cortex. Technique combines sucrose percoll fractionation of a synaptically rich sample (SN) and TRAP tagged ribosome IP (PreIP and PostIP). This experiment uses pan neuronal SNAP25 mice and a cortical dissection. Overall design: Three replicates of four samples.
Publication Title
Transcriptomic Analysis of Ribosome-Bound mRNA in Cortical Neurites <i>In Vivo</i>.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
To assess the role of the aryl hydrocarbon receptor (AHR) receptor in dendritic epidermal T cells (DETC), we sorted DETC from 2 weeks old mice homozygous and heterozygous for AHR-knockout. While DETC are not maintained in the epidermis of mice with a homozygous AHR-knockout, those in heterozygous mice devellop normally. The age at 2 weeks is critical for the DETC establishment and the peak time of the so-called proliferation burst of DETC in wildtype mice. DETC were identified in epidermal cell suspension by expression of the gamma-delta T cell receptor. The DETC proportion of live epidermal cells was between 10-15 % in Ahr-het and 2-4 % in Ahr-ko mice. After FACS-sorting to a purity of 90-98 %, DETC were lysed and their RNA was extracted. Three RNA samples for each genotype were generated, by pooling the RNA of 2-3 mice for each sample. RNA was processed and hybridized to Applied BiosystemsTM ClariomTM S Mouse Gene Expression Microarrays. Using the Software package R the data were normalized using the Robust Multichip Average algorithm (RMA) and significance of differentially regulated genes was assessed by the False Discovery Rate (FDR) using the Benjamini and Hochberg’s method.
Publication Title
The small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal gamma delta T cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of differentiated Caco-2 intestinal epithelial cell line cocultured with probiotics L. acidophilus NCFM, B. lactis 420, L. salivarius Ls-33 bacterial cells or treated with cell-free supernatant, and with E. coli O157:H7 cell-free supernatant. Lactobacillus and Bifidobacterium are important genera suggested to be beneficial for human health and E. coli O157:H7 is a pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. Results provide insight into the mechanisms underlying the beneficial effects of probiotics on intestinal epithelial cells and a comparison to pathogenic E. coli.
Publication Title
Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli.
Sample Metadata Fields
No sample metadata fields
View Samples SRP065508- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the mRNAs bound to ribosomes in peripheral astrocyte processes, thus suggesting local translation in astrocytes. Overall design: Isolation of a synaptoneurosome fraction from mouse cortex in which Astrocyte ribosomes were labeled with eGFP. Immunoprecipitation of GFP from this fraction to obtain astrocyte ribosomes away from the cell body. Performed RNA seq on these purified ribosomes and their bound mRNAs.
Publication Title
Astrocytes locally translate transcripts in their peripheral processes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons. Overall design: Human fibroblasts were reprogrammed by microRNAs miR-9/9* and miR-124 (miNs). To profile transcriptome of the reprogrammed cells, mRNA were isolated from miNs day 30 and starting fibroblasts.
Publication Title
MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Skeletal muscle is a metabolic active tissue that secretes various proteins. These so called myokines act auto-, para- and endocrine affecting muscle physiology and exert systemic effects on other tissues and organs. Myokines are also described to play a crucial role in the pathophysiology of metabolic diseases.
Publication Title
Secretome profiling of primary human skeletal muscle cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We performed whole-genome gene expression profiling in Pik3cg-/- mice and subsequent gene ontology clustering of differentially expressed genes compared to wild type mice, in order to investigate the role of Pik3cg in platelet membrane biogenesis and blood coagulation.
Publication Title
Maps of open chromatin guide the functional follow-up of genome-wide association signals: application to hematological traits.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory. Overall design: Biological replicates: Fear conditioned: n=14, No shock controls: n=4, Home cage controls:n=3. The contents 10 dVenus+ and 10 dVenus- cells were aspirated from each animal (biological replicate)
Publication Title
Engram-specific transcriptome profiling of contextual memory consolidation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples