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SRP077927
Mus musculus
10 Downloadable Samples
Illumina HiSeq 2000
Description
Clonal cellular variance often confounds reproducibility of forward and reverse genetic studies. We developed combinatorial approaches for whole genome saturated mutagenesis using haploid murine ES cells to permit induction and reversion of genetic mutations. Using these systems, we created a biobank with over 100000 individual ES cell lines with repairable and genetically bar coded mutations targeting 16950 genes. This biobank termed “Haplobank” is freely available. In addition, we developed a genetic color coding system for rapid repair of mutations and direct functional validation in sister clones. Using this system, we report functional validation of essential ES cell genes. We also identified phospholipase16G as a key pathway for cytotoxicity of human rhinoviruses, the most frequent cause of the common cold. Moreover, we derived 3D blood vessel organoids from haploid ES cells, combining conditional mutagenesis in haploid ES cells with tissue engineering. We identified multiple novel genes, such as Connexin43/Gja1, in blood vessel formation and tip cell specification in vitro and also in vivo. Taken together, we develop a conditional homozygous ES cell resource for the community to empower controlled genetic studies in murine ES cells and tissues derived from it. Overall design: RNA-Seq was carried out using standard protocols. https://www.haplobank.at/ecommerce/control/haplobank_resource
Publication Title
Comparative glycoproteomics of stem cells identifies new players in ricin toxicity.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The biological mechanisms by which cerebral aneurysms emerge, enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays.
Publication Title
Transcriptome-wide characterization of gene expression associated with unruptured intracranial aneurysms.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ablation of the mouse gene for Onecut-2 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here, we examine postnatal development of these Onecut-2 knockout mice, especially the critical period prior to weaning. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in the Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression.
Publication Title
Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2a-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Overall design: Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
Publication Title
Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adenosine, prostaglandin E2, or increased intracellular cyclic AMP concentration each elicit potent anti-inflammatory events in human neutrophils by inhibiting functions such as phagocytosis, superoxide production, adhesion and cytokine release. However, the endogenous molecular pathways mediating these actions are poorly understood. In the present study, we examined their impact on the gene expression profile of stimulated neutrophils. We have identified a set of genes that may be part of important resolution pathways that interfere with cell activation. Identification of these pathways will improve understanding of the capacity of tissues to terminate inflammatory responses and contribute to the development of therapeutic strategies based on endogenous resolution
Publication Title
Impact of anti-inflammatory agents on the gene expression profile of stimulated human neutrophils: unraveling endogenous resolution pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Publication Title
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 12 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
As polyphenols are exerting a broad spectrum of metabolic effects, we hypothesize that feeding of GSGME might influence other metabolic pathways in the liver which could account for the positive effects of GSGME observed in cows during early lactation. In order to investigate this hypothesis, we used using a genome-wide transcript profiling technique to explore changes in the hepatic transcriptome of cows supplemented with GSGME during the transition period. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts (fold change > 1.3 or < -1.3, P < 0.05), from which 156 (155 mRNAs, 1 miRNA) were up- and 51 (43 mRNAs, 8 miRNAs) were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation, such as M phase, cell cycle phase, mitotic cell phase and microtubule cytoskeleton and the most enriched KEGG database pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that 13 genes (XBP1, HSPA5, HERPUD1, DNAJC5G, CALR, PDIA4, DNAJB11, PHLDA1, PPP1R3C, GADD45B, BAG3, HYOU1, MANF) are involved in ER stress-induced UPR. Moreover, several of the down-regulated mRNAs, like CXCL14 and CCL3L1L and the acute phase protein SAA4, play an important role in inflammatory processes. Accordingly, protein folding, response to unfolded protein, response to protein stimulus, unfolded protein binding, chemokine activity, chemokine receptor binding and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Collectively, our findings from transcriptome analysis of down-regulated mRNAs and functional analysis of mRNAs targeted by the up-regulated mir-376c clearly indicate that GSGME is able to inhibit inflammatory processes and ER stress in the liver of dairy cows during early lactation. Moreover, our findings indicate that at least some of the GSGME effects on the hepatic transcriptome of dairy cows are mediated by miRNA-mRNA interactions.
Publication Title
Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was performed to check that ESR1 and BMI1 are biologically active after lentiviral transduction of primary human mammary epithelial cells (HMECs) with lentiviral vectors expressing ESR1 and BMI1 from the human PGK promoter. ESR1 targets like PGR, PRLR and GREB1, but not TFF1 and XBP1, were induced by estradiol in the ESR1-expressing cells. BMI1 targets like BMI1, NEFL and CCND2 were repressed in the BMI1-expressing cells. BMI1 suppressed genes associated with squamous and neural differentiation in the ESR1 plus BMI1-expressing cells.
Publication Title
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.
Publication Title
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mind-body practices that elicit the relaxation response (RR) have been used worldwide for millennia to prevent and treat disease. The RR is believed to be the counterpart to stress response and is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. Individuals experiencing chronic psychological stress have the opposite pattern of physiology and a characteristic transcriptional profile. We hypothesized that consistent, long-term practice of RR techniques results in characteristic changes in gene expression. We tested this hypothesis by assessing the transcriptional profile of whole blood in healthy, long-term practitioners of daily RR practice (group M) in comparison to healthy controls (group N1). The signature obtained has been validated on new subject data.
Publication Title
Genomic counter-stress changes induced by the relaxation response.
Sample Metadata Fields
No sample metadata fields
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