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SRP186406
Homo sapiens
63 Downloadable Samples
NextSeq 500
Description
Background and aims: Hepatitis C virus (HCV) infection is a major cause of liver disease including steatosis, fibrosis and liver cancer. Viral cure cannot fully eliminate the risk of disease progression and hepatocellular carcinoma (HCC) in advanced liver disease. The mechanisms for establishment of infection, liver disease progression and hepatocarcinogenesis are only partially understood. To address these questions, we probed the functional proteogenomic architecture of HCV infection within a hepatocyte-model. Methods: Time-resolved HCV infection of hepatocyte-like cells was analyzed by RNA sequencing, proteomics, metabolomics, and leveraged by integrative genomic analyses. Using differential expression, gene set enrichment analyses, and protein-protein interaction mapping we identified pathways relevant for liver disease pathogenesis that we validated in livers of 216 cirrhotic patients with HCV. Results: We uncovered marked changes in the protein expression of gene sets involved in innate immunity, metabolism and hepatocarcinogenesis. In infected cells, HCV enhances glucose metabolism and creates a Warburg-like shift of the lactate flux. HCV infection impaired the formation of peroxisomes -organelles required for long-chain fatty acid oxidation- causing intracellular fatty acid accumulation, which is a hallmark of non-alcoholic fatty liver disease (NAFLD). Ex vivo studies confirmed perturbed peroxisomes and revealed an association of hepatic catalase expression with clinical outcomes and phenotypes in HCV-associated cirrhosis, NAFLD and HCC cohorts. Conclusion: Our integrative analyses uncover how HCV perturbs the hepatocyte cell circuits to drive chronic liver disease and hepatocarcinogenesis. This proteogenomic atlas of HCV infection provides a model for the discovery of novel drivers for viral- and non-viral induced liver disease. Overall design: mRNA profiles of either mock or HCV-infected Huh7.5.1dif cells, performed in triplicates and collected every day between days 0 and 10 post infection. HCV infection reached plateau at day 7 post infection (pi). After day 7 pi unspecific effects cannot be excluded.
Publication Title
Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), which functions to increase ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2, Bric-Ã -brac (Bab), Apterous (Ap) and Dachshund (Dac), constitute a functionally conserved transcription factor (TF) network, previously shown to pattern the segmentation of the leg, that patterns the developing olfactory tissue. Precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines Overall design: Time-course RNAseq across 4 developmental stages, inlcuding flies mutant for rotund gene (rn), heterozygotes and wildtype
Publication Title
Comparative analysis of behavioral and transcriptional variation underlying CO<sub>2</sub> sensory neuron function and development in Drosophila.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA. Likewise, knockdown of ZXDC1 restricts the induced expression of these markers. We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
Publication Title
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Transcriptome analysis of two Ph+ acute lymphoblastic leukemia cell lines after doxycycline induced silencing of MYB.
Publication Title
Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph<sup>+</sup> Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 293 Downloadable Samples
- Illumina HiSeq 2000
Description
In the diploid genome, genes come in two copies, which can have different DNA sequence and where one is maternal and one is paternal. In a particular cell, a gene could potentially be expressed from both copies (biallelic expression) or only one (monoallelic). We performed RNA-Sequencing on individual cells, from zygote to the cells of the late blastocyst, and also individual cells from the adult liver. Using first generation crosses between two distantly related mouse strains, CAST/Ei and C57BL/6, we determined the expression separately from the maternal and paternal alleles. We found that half of the genes were expressed by only one allele, randomly so that some cells would express the paternal allele, some the maternal and a few cell both alleles. We also observed the spread of the progressive inactivation of the paternal X chromosome. Overall design: First generation mouse strain crosses were used to study monoallelic expression on the single cell level
Publication Title
Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Neural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. Overall design: Examination of dorsal and ventral regions from 4 replicate samples each containing pooled data from 3-4 mice
Publication Title
Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In a whole-transcriptome study, cellular responses of DCs and macrophages confronted with the fungi A. fumigatus, platelet rich plasma (PRP) or the combination of A.fumigatus and PRP were investigated. Therefore DCs and macrophages of three independent donors were harvested after 6 hours co-culture with A. fumigatus, platelet rich plasma (PRP) or the combination of A.fumigatus and PRP and analyzed with Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a cell type dependent clustering. Only little effects were obeserved by addition of PRP. Furthermore a clustering of A.fumigatus stimulated cells whether PRP was present or not, was observed. However, significant differences in the immune response of A.fumigauts stimuled DC and macrophages were determined.
Publication Title
Influence of Platelet-rich Plasma on the immune response of human monocyte-derived dendritic cells and macrophages stimulated with Aspergillus fumigatus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- NextSeq 500
Description
The unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation. Overall design: We generated stocks of lentiviral vector bearing one the following three M-EBOV GPs: founder, A82V, and A82V/T230A. These viral stocks were used to challenge MDDCs from two healthy, anonymous human donors. Stimulated MDDCs were harvested at 1, 2, 4, and 6 hours after viral addition. Gene expression in M-EBOV GP challenged MDDCs was compared to a unstimulated control.
Publication Title
Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrixs HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples