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Homo sapiens
40 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
c-Myc controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state and a shorter survival time compared to the MYC-low subgroup. To define classifier expression signature, we selected a group of 10 MYC targets transcripts which expression is increased in the MYC-high group and 6 transcripts increased in the MYC-low group. We validated the ability of these markers panel to identify MYC-high patient-derived xenografts from both: discovery and validation cohorts as well as primary cells cultures from the same patients. We then showed that cells from MYC-high patients are more sensitive to JQ1 treatment compared to MYC-low cells, in both monolayer and 3D cultured spheroids, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics.
Publication Title
Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts.
Sample Metadata Fields
Disease
View Samples- Hordeum vulgare, Hordeum vulgare subsp. spontaneum
- 18 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
The bird cherry-oat aphid (Rhopalosiphum padi L.) (Homoptera: Aphididae) is an important pest on cereals causing plant growth reduction but no specific leaf symptoms. Breeding of barley (Hordeum vulgare L.) for R. padi resistance shows that there are several resistance genes involved, reducing aphid growth. In an attempt to identify candidate sequences for resistance-related genes, we performed a microarray analysis of gene expression after two days of aphid infestation in two susceptible barley lines and two genotypes with partial resistance. One of the four lines is a descendant of two of the other genotypes. The analysis revealed large differences in gene induction between the four lines, indicating substantial variation in response even between closely related genotypes. Genes induced in the aphid-infested tissue were mainly related to defence, primary metabolism and signalling. Only twenty-four genes were induced in all lines, none of them related to oxidative stress or secondary metabolism. Few genes were down-regulated and none of those was common to all four lines. There were differences in aphid-induced gene regulation between resistant and susceptible lines, and results from control plants without aphids also revealed differences in constitutive gene expression between the two types of lines. Candidate sequences for both induced and constitutive resistance factors have been identified, among them a proteinase inhibitor, a Ser/Thr kinase and several thionins.
Publication Title
Microarray analysis of the interaction between the aphid Rhopalosiphum padi and host plants reveals both differences and similarities between susceptible and partially resistant barley lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health.
Publication Title
The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Overall design: Transcriptional activity at the HoxD locus in the murine developing gut at E13, Differential gene expression analysis along the murine developing gut
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP018708- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in developing caeca at E13.5 Overall design: Transcriptional activity at the HoxD locus in developing caeca at E13.5
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Adipose tissue stromal cells contribute to the regulation of adipose tissue in lean and obese states. Myeloid cells such as adipose tissue macrophages (ATMs) and dendritic cells (ATDCs) undergo both quantitative and qualitative changes with obesity. Due to similarity in markers the identify of adipose tissue dendritic cells and macrophages has been elusive. We have refined prior protocols to unambiguously discern ATM and ATDC in mice. We used microarrays to compare the profiles of ATMs and ATDC from gonadal adipose tissue from lean, obese, and formerly obese mice. We also isolated preadipocytes (PA) from lean and obese mice for comparison.
Publication Title
Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
IL-17A is a pro-inflammatory cytokine that promotes host defense against infections and contributes to the pathogenesis of chronic inflammatory diseases. Dendritic cells (DC) are antigen-presenting cells responsible for adaptive immune responses. Here, we report that IL-17A induces intense remodeling of lipid metabolism in human monocyte-derived DC, as revealed by microarrays analysis. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases.
Publication Title
Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Publication Title
Mesenchymal stem cell features of Ewing tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs. immature neurons. We used immature (d0) and mature (d6) LUHMES cells (dopaminergic human neurons) to provide initial answers to these questions. Transcriptome profiling and characterization of energy metabolism suggested a switch from predominantly glycolytic energy generation to a more pronounced contribution of the tricarboxylic acid cycle (TCA) during neuronal maturation. Therefore, we used pulsed stable isotope-resolved metabolomics (pSIRM) to determine intracellular metabolite pool sizes (concentrations), and isotopically non-stationary 13C-metabolic flux analysis (INST 13C MFA) to calculate metabolic fluxes. We found that d0 cells mainly use glutamine to fuel the TCA. Furthermore, they rely on extracellular pyruvate to allow continuous growth. This metabolic situation does not allow for mitochondrial or glycolytic spare capacity, i.e. the ability to adapt energy generation to altered needs. Accordingly, neuronal precursor cells displayed a higher sensitivity to several mitochondrial toxicants than mature neurons differentiated from them. In summary, this study shows that precursor cells lose their glutamine dependency during differentiation while they gain flexibility of energy generation and thereby increase their resistance to low concentrations of mitochondrial toxicants.
Publication Title
Stage-specific metabolic features of differentiating neurons: Implications for toxicant sensitivity.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples