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SRP040018
Danio rerio
16 Downloadable Samples
IlluminaHiSeq2500
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
- 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
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
We use the Tlr2 mutant of zebrafish embryos model to study the transcriptome response to Mycobacterium marinum infection. We injected M.marinum into the caudal vein at 28 hours post fertilization and took samples at 4 days post infection. Overall design: This deep sequence study was designed to determine the gene expression profile in the Tlr2 mutant and heterozygote by M.marinum infection. RNA was isolated at 4 days post infection. Tlr2 mutants and heterozygotes zebrafish embryos were micro-injected into the caudal vein with 150CFU M.marinum, or PBS as a control at 28 hours post fertilization. After injections embryso were transerred into fresh egg water and incubated at 28 degree. At 4 days post infection triplicateds of 10 embryos per condition were snapfrozen in liquid nitogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Infection and RNA-seq analysis of a zebrafish tlr2 mutant shows a broad function of this toll-like receptor in transcriptional and metabolic control and defense to Mycobacterium marinum infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000
Description
Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion.
Publication Title
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina Genome Analyzer
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
Illumina Genome Analyzer, Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are significally expressed by DNA damage and and are non- coding.
Publication Title
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long noncoding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cellular transformation. However, the underlying mechanisms remain poorly understood. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We found that LINC-PINT acts as tumor suppressor lncRNA. Its expression is downregulated in multiple types of cancer and correlates with good prognosis in lung adenocarcinoma. LINC-PINT inhibits the migration capacity and invasive phenotype of cancer cells in vitro and in vivo, and it does so by repressing a proinvasion gene signature in a PRC2-dependent manner. By applying cross-species conservation analysis combined with functional experimental validations we found that the function of LINC-PINT is highly dependent on a short sequence conserved across mammals, sequence that mediates the interaction with PRC2. We propose that LINC-PINT may function as a molecular exchanger that provides PRC2 to active gene promoters for their silencing, mechanisms that could be shared by other PRC2-interacting lncRNAs.
Publication Title
The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus, Homo sapiens
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Sample Metadata Fields
Specimen part, Disease, Cell line, Treatment, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
It has been recently shown that the transcription factor p53 induces the expression of multiple lincRNAs. However, relatively little is known about the role that lincRNAs play in this pathway. Here we characterize a lincRNA named PINT (p53 Induced Noncoding Transcript). We show that PINT is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, PINT promotes cell proliferation and survival by regulating the expression of genes of TGF-beta, MAPK and p53 pathways. PINT is a nuclear lincRNA that directly interacts with Polycomb Repressive Complex 2 (PRC2), being required for PRC2 targeting of specific genes for repression. Furthermore, PINT functional activity is dependent on PRC2 expression, representing a connection between the p53 pathway and epigenetic regulation by PRC2. We have also identified PINT human ortholog (hPINT), which presents suggestive analogies with the mouse lincRNA. hPINT is similarly regulated by p53, and its expression correlates significantly with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, hPINT is significantly downregulated in colon cancer, representing a novel tumor suppressor candidate. Our results not only help our understanding of the role of p53 and lincRNAs in cancer, but also contribute to the open debate regarding the utility of mouse models for the study of lincRNAs.
Publication Title
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Sample Metadata Fields
Specimen part, Treatment
View Samples