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GSE48101
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Access to an unlimited number of human pancreatic beta cells represents a major challenge in the field of diabetes to better dissect human beta cell functions and to make significant progress in drug discovery and cell replacement therapies. We previously reported the generation of the EndoC-bH1 human beta cell line that was generated by targeted oncogenesis in human fetal pancreases followed by in vivo cell differentiation in mice. Such cell line displayed many functional properties of adult beta cells. Here we devised a novel strategy to generate conditionally immortalized human beta cell lines based on CRE-mediated excision of immortalizing transgenes. The resulting EndoC-bH2 cell line can be massively amplified in vitro. Transgenes are next efficiently excised upon CRE expression leading to cell proliferation arrest and strong enhancement of beta cell specific features such as insulin expression, content and secretion. Excised EndoC-bH2 cells are close to authentic human beta cells and represent a unique tool to further study beta cell function and to understand why adult human beta cells are refractory to proliferation and how to achieve drug-dependent mobilization towards beta cell expansion.
Publication Title
Development of a conditionally immortalized human pancreatic β cell line.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes, and precursors for signalling molecules. Here we show that these important biological compounds also regulate gene expression by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPAR/. Our data indicates that these activities of LCFA are mediated by FABP5, a protein that delivers ligands from the cytosol to nuclear PPAR/. Both saturated and unsaturated LCFA (SLCFA, ULCFA) tightly bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPAR/ pathway. By concomitantly promoting the activation of RAR and inhibiting the activity of PPAR/, SLCFA suppress the growth and oncogenic properties of FABP5-expressing carcinoma cells both in cultured cells and in vivo.
Publication Title
Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The irreversible decarboxylation step, which commits 2-oxo acids to the Ehrlich pathway, was initially attributed to pyruvate decarboxylase. However, the yeast genome was shown to harbour no fewer than 5 genes that show sequence similarity with thiamine-diphosphate dependent decarboxylase genes. Three of these (PDC1, PDC5 and PDC6) encode pyruvate decarboxylases { while ARO10 and THI3 represent alternative candidates for Ehrlich-pathway decarboxylases.
Publication Title
The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Compared to other fish models, miRNAs are currently most extensively studied and identified in zebrafish. Approximately 415 dre-miRNAs have been identified and several articles have studied some aspect of miRNA function in zebrafish such as their role in basic development and in disease pathways. However, this field of research is in its infancy and the function of several dre-miRNAs, as well as their tissue-specific expression profile, are yet to be defined. In this study, the liver and gut were dissected (wildtype/untreated fish), total and small RNA were extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing (HTS) using standard approaches. We carried out differential expression (DE) analysis and compared liver miRNA expression to gut using established bioinformatics pipelines. Through bioinformatics analysis, known and putative novel miRNAs were identified. Finally, we constructed a “miRNA matrix” that connects both total RNA-Seq and miRNA-Seq. Overall design: Examination of transcriptome in an in vivo model organism in two defined tissues, liver and gut.
Publication Title
Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (<i>Danio rerio</i>).
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Multiciliated cells are crucial for fluid and ion transport in epithelia of a variety of organs and their impaired development and function are seen in human diseases affecting the brain, respiratory, and reproductive tracts. Multiciliogenesis requires activation of a specialized transcription program coupled to complex cytoplasmic events that lead to large-scale centriole amplification to generate multicilia. Yet, it remains unclear how these events are coordinated to initiate multiciliogenesis in epithelial progenitors. Here we identify an unsuspected mechanism orchestrated by the transcription factor E2f4 essential to integrate these processes. We show that after inducing a transcriptional program of centriole biogenesis, E2f4 translocates to the cytoplasm to become a core component of structures classically identified as fibrous granules (FG), acting as organizing centers for deuterosome assembly and centriole amplification. Remarkably, loss of cytoplasmic E2f4 prevents FG aggregation, deuterosome assembly and multicilia formation even when E2f4s transcriptional function is preserved. Moreover, in E2f4-deficient cells multiciliogenesis is rescued only if both nuclear and cytoplasmic E2f4 activities are restored. Thus, E2f4 integrates previously unrelated nuclear and cytoplasmic events of the multiciliated cell program.
Publication Title
Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Analysis of alveolar macrophage gene expression in C57BL6 wild-type and RAGE null mice exposed to cigarette smoke Overall design: 4 groups of 3-4 mice at two exposure time points (7-day and 4 month), 31 samples total
Publication Title
RAGE is a Critical Mediator of Pulmonary Oxidative Stress, Alveolar Macrophage Activation and Emphysema in Response to Cigarette Smoke.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Rattus norvegicus
- 23 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these hypertension-related elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study.
Publication Title
The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Publication Title
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs, are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops disease that resembles human cancer. Using zebrafish as systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 21 day exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6,188 mRNAs and 15 miRNAs were differently expressed (q = 0.1). By analyzing human orthologs of the DE zebrafish genes signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome in adult zebrafish and has the potential to cause adverse outcomes including cancer. Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Publication Title
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene Expression Array (primeview)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples