Filters
Technology
Platform
SRP040018
Danio rerio
16 Downloadable Samples
Illumina HiSeq 2500
Description
Type 2 Diabetes, obesity and metabolic syndrome are pathologies impacting a large population worldwide where insulin resistance plays a central role. These pathologies are usually associated to a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia) what diminishes the concentration of key downstream elements causing insulin resistance. The complexity of the study of insulin resistance relies on the heterogeneity of the metabolic states where it’s observed. In consequence, animal models for the study of insulin resistance, can not completely recapitulate the metabolic status of insulin resistant humans, what is translated in contradictory observations. To contribute to the understanding of the mechanisms triggering insulin resistance we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish embryos appeared to be sensitive to human recombinant insulin, becoming insulin resistant when exposed to a high dose of the hormone, as confirmed by glucose measurements. Moreover RNAseq-based transcriptomic profiling of these embryos revealed a strong down regulation of a number of immune relevant genes as a consequences of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator ptpn6 appeared to be up regulated in insulin resistant embryos. Knockdown of ptpn6 showed to counteract the observed down regulation of the immune system and insulin signalling pathways effects at the transcriptional level caused by hyperinsulinemia. These results show that ptpn6 is a mediator of the metabolic switch between insulin sensitive and insulin resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated it suitability to discover novel regulators of insulin resistance. In addition, our data will be very useful to further study the function of immunological determinants in a non-obese model system. Overall design: 16 samples in total were analyzed. 4 replicates from control samples (injected with PBS) and 4 replicates of insulin injected samples at 0.5 hpi and 4 hpi. In each sample 10 embryos were pooled.
Publication Title
Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
We use the zebrafish embryo model to study the innate immune response against polystyrene particles. Therefore, we injected 700nm polystyrene into the yolk at 2 dpf and took samples at 1 and 3 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by polystyrene particle toxicity. RNA was isolated from embryos at 1 and 3 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2dpf) with 1nl of 5mg/ml of 700nm red fluorescent polystyrene particles suspended in PVP (Polyvinylpyrrolidone) (n=3), mock injected with pvp (n=2), or Non-injected as a control (n=3). After injections embryos were transferred into fresh egg water and incubated at 28°C. At 1 and 3 days post injection 10 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Cardiomyopathies-associated metabolic pathologies (e.g. T2D and insulin resistance) are a leading cause of mortality. It is known that the association between the pathologies works in both directions, where heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulin regulated glucose transporters and the development of cardiomyopathies, we set out to study GLUT12. GLUT12 is a novel insulin regulated GLUT expressed in the main insulin sensitive tissues such as cardiac and skeletal muscle and adipose tissue. This study investigates the role of GLUT12 in heart failure and diabetes by developing a model for glut12 deficiency in zebrafish. Overall design: 6 samples in total were analyzed. 3 replicates from control samples (injected with contol MO) and 3 replicates from glut12 morphant samples (injected with glut12 splice MO). In each sample 10 embryos were pooled.
Publication Title
GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Transcriptional profiling of the zebrafish embryonic host response to a systemic bacterial infection with Salmonella typhimurium (strain SL1027); comparison between traf6 knock-down and control morpholino treated embryos. Overall design: All infection experiments were performed using mixed egg clutches of ABxTL strain zebrafish. Embryos injected with traf6 morpholino or a 5bp mismatch control morpholino were staged at 27 hours post fertilization (hpf) by morphological criteria and approximately 250 cfu of DsRed expressing Salmonella bacteria were injected into the caudal vein close to the urogenital opening. As a control an equal volume of PBS was likewise injected. Pools of 20-40 infected and control embryos were collected 8 hours post infection (hpi). The whole procedure was preformed in triplicate on separate days. Total RNA of the biological triplicates was pooled using equal amounts of RNA prior to RNAseq library preparation.
Publication Title
Transcriptome analysis of Traf6 function in the innate immune response of zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
We compared Agilent custom made expression microarrays with Illumina deep sequencing for RNA analysis of zebrafish embryos 5 days post fertilization, showing as expected a high degree of correlation of expression of a common set of 15,927 genes for untreated fish. The transcriptomes were also compared for fish injected in the yolk with Mycobacterium marinum Overall design: This RNA deep sequencing study was designed to determine the gene expression profile of zebrafish embryos 5 days post fertilization. We also have compared expression with embryos that were injected with Mycobacterium marinum in the yolk at 2 hours post fertilization. After injections embryos were transferred into fresh egg water and incubated at 28°C. 150 embryos of mock-injected embryos or 200 embryos injected with 12 CFU bacteria were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
PPAR is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPAR in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPAR, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPAR as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPAR agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPAR deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPAR sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense.
Publication Title
Systemic analysis of PPARγ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Publication Title
Comparison of gene expression profiles between human and mouse monocyte subsets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Naturally occurring CD25+CD4+ regulatory T cells (T reg cells) are currently intensively characterized because of their major importance in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy. Originally, CD4+ T reg cells were identified exclusively by the constitutive expression of CD25, and many in vivo experiments have been performed using depleting antibodies directed against CD25. However, both the existence of CD25 T reg cells, especially within peripheral tissues, as well as the expression of CD25 on activated conventional T cells, which precludes discrimination between T reg cells and activated conventional T cells, limits the interpretation of data obtained by the use of anti-CD25 depleting antibodies. The most specific T reg cell marker currently known is the forkhead box transcription factor Foxp3, which has been shown to be expressed specifically in mouse CD4+ T reg cells and acts as a master switch in the regulation of their development and function. To address the question of the in vivo role of T reg cells in immunopathology, we have generated bacterial artificial chromosome (BAC)transgenic mice termed depletion of regulatory T cell (DEREG) mice, which express a diphtheria toxin receptor (DTR) enhanced GFP (eGFP) fusion protein under the control of the foxp3 locus, allowing both detection and inducible depletion of Foxp3+ T reg cells. The gene expression profile of both CD4+eGFP+FoxP3+ and CD4+eGFPnegFoxP3neg cells isolated from DEREG mice was here analyzed by micro array.
Publication Title
Immunostimulatory RNA blocks suppression by regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation.
Publication Title
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of beige cells from murine white fat depots.
Publication Title
Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.
Sample Metadata Fields
Cell line
View Samples