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Mus musculus
2 Downloadable Samples
Illumina HiSeq 1000
Description
GPR68 is an essential flow sensor in arteriolar endothelium, and is a critical signaling component in cardiovascular pathophysiology Overall design: RNAseq of cells from mesenteric endothelium of mice plus and minus GPR68
Publication Title
GPR68 Senses Flow and Is Essential for Vascular Physiology.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 170 Downloadable Samples
- Illumina HiSeq 1000
Description
Purpose: Single-cell whole transcriptome sequencing was used to better understand the mechanism of action of our Dyrk1a inhibitor''s proliferation of pancreatic islets. Methods: primary pancreatic islets were isolated, cultured, and stimulated with either 0.1% DMSO or 3 µM GNF4877. Single cells were captured and cDNA isolated on a Fluidigm C1 instrument. Sequencing libraries were made with Nextera XT reagents (Illumina) and single-end 50 bp reads were generated on an Illumina HiSeq 1000. Reads were mapped to the rat transcriptome. Results: Consistent with GNF4877 eliciting beta cell proliferation, we observed an increase in the number of beta cells co-expressing insulin 1 and genes involved in cell cycle including the M phase marker Cyclin B1. Comparison of Cyclin B1 expressing cells from GNF4877-treated islets to beta cells from DMSO-treated islets further revealed a significant increase expression of genes associated with full cell cycle progression and enrichment of Gene Ontology (GO) categories for proliferation. Conclusions: Since only a small subset of islet cells proliferate when stimulated with GNF4877, single-cell transcriptome sequencing allowed us to examine expression of genes co-regulated with known proliferation markers and will hopefully allow us to characterize beta cell subsets which are responsive to proliferation-associated therapies. Overall design: 84 GNF4877-treated and 86 DMSO-treated rat islet cells containing greater than 100,000 mapped sequencing reads per cell and having a single verified cell per port were compared
Publication Title
Inhibition of DYRK1A and GSK3B induces human β-cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
About 15% of the TG26 mice develop lymphoma. HIV protein expression is observed, particularly the protein p17/Matrix. Total cellular RNA from spleen and lymph nodes from 3 groups of animals: FVB/N controls (n=3), Tg26 asymptomatic (n=6), and Tg26 with lymphoma (n=6). Results provide insights into the gene expression program in animals with lymphoma.
Publication Title
Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase (HPRT), suggesting an elevated gene-dosage of HPRT in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-Diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy.
Publication Title
Identification of Selective Lead Compounds for Treatment of High-Ploidy Breast Cancer.
Sample Metadata Fields
Cell line
View Samples
SRP102949- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We have generated RNA-seq of ILC2 progenitors form WT bone marrow mice. Overall design: Sorted ILC2p from 8 week-old mice were analysed in RNA-seq. Each replicate is a pool of 8 mice.
Publication Title
Androgen signaling negatively controls group 2 innate lymphoid cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Oxidative injury and inflammation have been implicated in the genesis of hypertension but the mechanisms involved are not fully understood. We describe a new pathway in which angiotensin II promotes dendritic cell (DC) activation of T cells and ultimately hypertension. NADPH oxidase-dependent superoxide production is increased 5-fold in DCs isolated from hypertensive mice as compared to sham-treated mice. This is associated with DC accumulation of protein-isoketal adducts and production of IL-6, IL-1 and IL-23. DCs from hypertensive mice but not sham mice promote survival and proliferation of CD8+ T cells in culture. Chemically diverse isoketal scavengers not only prevent activation and immunogenicity of DCs, but also attenuate angiotensin II-induced hypertension. Moreover, adaptive transfer of DCs from hypertensive mice prime development of hypertension in response to a subpressor dose of angiotensin II. Exposure of DCs to tert butyl hypdroperoxide promoted isoketal formation, DC stimulation of CD8+ T cell proliferation and primed hypertension in response to low dose angiotensin II. Serum isoprostanes, precursors to isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension. These studies show that angiotensin II-induced hypertension activates DCs, in large part by causing superoxide production and formation of isoketals. They define a new mechanism of hypertension and identify a potential new therapeutic approach for this disease.
Publication Title
DC isoketal-modified proteins activate T cells and promote hypertension.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
IgE plays an essential role in the pathogenesis of allergies and its production is strongly regulated. A transient IgE germinal center phase and lack of IgE memory cells limit the generation of pathogenic IgE, but this can be overcome by sequential switching of IgG1 cells to IgE. We investigated which population of IgG1 cells can give rise to IgE-producing cells in memory responses. We identified three populations of IgG1 memory B cells (DP:CD73+CD80+, SP:CD73-CD80+, DN:CD73-CD80-) that generate IgE plasma cells of high or low affinity, but none gives rise to IgE germinal center cells or IgE memory cells. The two memory IgG1 populations differ however in their ability to differentiate into IgG1 plasma cells and germinal center cells, and to expand the IgG1 memory B cell pool. To explore the molecular mechanisms that may explain the distinct functions of IgG1 memory B cell subsets we compared their expression by transcriptome analysis using next generation sequencing. Overall design: mRNA profiles of quadruplicates of double positive (DP:CD73+CD80+), single positive (SP:CD73-CD80+), double negative (DN:CD73-CD80-) IgG1 memory B cells along with IgG1 germinal center (GC) cells and naïve B cells were generated using Illumina high throughput sequencing.
Publication Title
IgG1 memory B cells keep the memory of IgE responses.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Publication Title
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE cells in these memory responses is particularly unclear. IgE B-cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B-cell receptor function and increased apoptosis. IgE GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B-cell differentiation fates: direct switching generates IgE GC cells, whereas sequential switching gives rise to IgE plasma cells. We propose a comprehensive model for the generation and memory of IgE responses.
Publication Title
The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response.
Sample Metadata Fields
Specimen part, Treatment
View Samples GSE40488- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells.
Sample Metadata Fields
Specimen part
View Samples