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GSE105288
Homo sapiens
44 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Renal cell carcinoma (RCC) is among the ten most common malignancies. By far, the most common histology is clear cell (ccRCC). The Cancer Genome Atlas and other large scale sequencing studies of ccRCC have been integral to the current understanding of molecular events underlying RCC and its biology. However, these data sets have focused on primary RCC which often demonstrates indolent behavior. In contrast, metastatic disease is the major cause of mortality associated with ccRCC. However, data sets examining metastatic tumor are sparse. We therefore undertook an integrative analysis of gene expression and DNA methylome profiling of metastatic ccRCC in addition to primary RCC and normal kidney. Integrative analysis of the methylome and transcriptome identified over 30 RCC specific genes whose mRNA expression inversely correlated with promoter methylation including several known targets of hypoxia inducible factors (HIFs). Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation. Collectively, our data provide novel insight into biology of aggressive RCC. Furthermore, they demonstrate a clear role for epigenetics in the promotion of HIF signaling and invasive phenotypes in renal cancer.
Publication Title
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Understanding gene expression changes during transformation from normal tissue to primary RCC and then to metastasis is important. Such analysis is pivotal for undertanding biology in renal cancer and also to unearth novel gene targets.
Publication Title
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
NextSeq 500
Description
Despite the prevalence and recognition of its detrimental impact, clinical complications of sepsis remain a major challenge. Here, we investigated the effects of myeloid ferritin heavy chain (FtH) in regulating the pathogenic sequelae of sepsis. We demonstrate that deletion of myeloid FtH leads to tolerance towards sepsis as evidenced by reduced serum cytokine levels, multi-organ dysfunction and subsequent mortality. We identified that such tolerance is predominantly mediated by the compensatory increase in circulating ferritin (ferritin light chain; FtL) in the absence of myeloid FtH. Our in vitro and in vivo studies indicate that prior exposure to ferritin provides significant tolerance to the septic process by restraining an otherwise dysregulated response to infection. These findings are mediated by an inhibitory action of ferritin on NF-?B activation and its downstream effects. Taken together, our findings suggest an essential immunomodulatory function for circulating ferritin and enhances our understanding of this acute phase reactant. Overall design: Total RNA were isolated from blood leukocytes of wild type FtH mice and Myeloid deficient FtH mice following sham and CLP surgery. Three biological replicates were considered for each genotype and surgery type.
Publication Title
Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 477 Downloadable Samples
- Illumina HiSeq 2500
Description
Neuronal diversity is a defining feature of the mammalian brain deemed necessary for realizing the complex function of the nervous system. In order to begin to understand the transcriptional basis of this diversity, we collected more than 170 neuronal and non-neuronal cell type-specific transcriptomes defined operationally by transgenic mouse lines and anatomical regions. The dataset indicates that the genes specifically expressed in neuronal cell types are biased toward long genes. We revealed that these long genes have higher capacities to be differentially expressed between cell types and thus assume an important role in diversification of the neuronal transcriptomes. Since mobile element insertions are the main cause of the gene elongations, we propose that exaptation of the inserted mobile elements significantly contributed to the neuronal diversity. Overall design: Examination of whole cell transcriptomes in 174 cell types.
Publication Title
Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Macaca mulatta
- 46 Downloadable Samples
- Rhesus Gene 1.0 ST Array (rhegene10st)
Description
Zika virus (ZIKV) is responsible for a major current outbreak in the Americas and has been causally associated with fetal microcephaly as well as Guillain-Barre syndrome in adults. However, the immune responses associated with controlling ZIKV replication remain poorly characterized. Here we report a detailed analysis of innate and adaptive immune responses following ZIKV infection in 16 rhesus monkeys. A robust proinflammatory innate immune response was observed within the first few days of infection, including upregulation of type 1 interferon, which correlated directly with viral loads. Immunomodulatory pathways, including IL-10 and TGF-, were also upregulated. ZIKV-specific neutralizing antibodies emerged rapidly by day 7 and correlated inversely with viral loads, which were undetectable in peripheral blood by day 6-10. In contrast, virus replication persisted in cerebrospinal fluid (CSF) for at least 21-42 days in 75% (3 of 4) of the monkeys that received the lowest dose of ZIKV tested, and ZIKV-specific antibodies were essentially undetectable in CSF. These data suggest that antibodies play a critical role in the rapid control of acute viremia in the periphery but were largely excluded from the central nervous system, allowing viral persistence at this immuonoprivileged site.
Publication Title
Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells. Overall design: B cells derived from control and CD19-Cre;Id3loxP/loxP mice were activated in vitro in the presence of LPS and IL-4 for 24 or 48 hours. RNA was isolated from naïve as well as activated control and CD19-Cre;Id3loxP/loxP mice and analyzed by RNA-seq, in duiplicate.
Publication Title
Id3 Orchestrates Germinal Center B Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A deletion in the CMAH gene in humans occurred approximately 3.5 million years ago. This resulted in the inactivation of the CMP-Neu5Ac hydroxylase enzyme, and hence, in the specific deficiency in N-glycolylneuraminic acid (Neu5Gc), a form of sialic acid, in all modern humans. Although there is evidence that this molecular milestone in the origin of humans may have led to the evolution of human-specific pathogens, how deficiency in Neu5Gc might alter progression of non-infectious human diseases remains unanswered. Here, we have investigated cardiac and skeletal muscle gene expression changes in mdx mice, a model of Duchenne muscular dystrophy (DMD), that do or do not carry the human-like inactivating mutation in the mouse Cmah gene. We have evidence that Neu5Gc-deficiency in humans might explain some of the discrepancies in the disease phenotype between mdx mice and DMD patients.
Publication Title
A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 1500
Description
Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and alterations in mRNA levels were analyzed. We identified three transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands, in the presence of three different “reprogramming” signals; high density immune complexes (IC), prostaglandin E2 (PGE2), or adenosine (Ado). All three of these cell populations produced higher levels of transcripts for IL-10, and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1Beta, IL-6, and IL-12. All three macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore we consider each to have immunoregulatory activity. This immunoregulatory activity occurred equally well in macrophages from stat6-deficient mice. The lack of STAT6 did not affect macrophages’ ability to reciprocally change cytokine production or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These immunoregulatory macrophages are transcriptionally and functionally related, and quite distinct from macrophages treated with IL-4.
Publication Title
The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 17 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
microRNAs play crucial roles in the early development of an organism. However the regulation of transcription through the action of microRNAs during the initial embyonic development has not been studied.
Publication Title
miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
Use NGS-transcriptome profiling (RNA-seq) to investigate deregulated genes involved in the proliferative effects of ID-8 and Harmine after hypoxia-induced damage in primary human proximal tubular epithelial cells (HPTECs) Overall design: Examination of differentially expressed genes in HPTECs treated with 1uM of ID-8; or 1uM of Harmine; or EGF in comparison to cells without treatment after 24 hours of hypoxia, in triplicates
Publication Title
A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation.
Sample Metadata Fields
Specimen part, Subject
View Samples