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SRP116047
Mus musculus
28 Downloadable Samples
Illumina HiSeq 1500
Description
While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and non-coding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently co-expressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels. Overall design: CTLL2 cells were grown in complete media for 24 hrs, and then stimulated with fresh B16F0 exosomes resuspended in PBS, to a final exosome concentration of 0.2 mg/ml. The transcriptome of untreated CTLL2 cells was assayed at 0, 0.5, 2, 4, and 8 hours after cells were placed in fresh media. There are 4 biological replicates at the 0 hour time point and 3 biological replicates at the 0.5, 2, 4, and 8 hour time points. The transcriptome of CTLL2 cells treated with B16F0 exosomes was assayed at 0.5, 2, 4, and 8 hours after addition of fresh media containing B16F0 exosomes. There were 3 biological replicates performed at each time point.
Publication Title
Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 83 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. Methods. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. Findings. There were no significant differences in gene expression for any transcript. Conclusions. Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.
Publication Title
Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer.
Sample Metadata Fields
Sex, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types.
Publication Title
Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Macaca mulatta
- 9 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Embryonic stem cells (ESCs) may be able to cure or alleviate the symptoms of various degenerative diseases. However, unresolved issues regarding apoptosis, maintaining function and tumor formation mean a prudent approach should be taken towards advancing ESCs into human clinical trials. The rhesus monkey provides the ideal model organism for developing strategies to prevent immune rejection and test the feasibility, safety and efficacy of ESC-based medical treatments. Transcriptional profiling of rhesus ESCs provides a foundation for future pre-clinical ESC research using non-human primates as the model organism. In this research we use microarray, immunocytochemistry, real-time and standard RT-PCR to characterize and transcriptionally profile rhesus monkey embryonic stem cells. We identify 367 rhesus monkey stemness genes, we demonstrate the high level (>85%) of conservation of rhesus monkey stemness gene expression across five different rhesus monkey embryonic stem cell lines, we demonstrate that rhesus monkey ESC lines maintain a pluripotent undifferentiated state over a wide range of Pou5f1 (Oct-4) expression levels and we compare rhesus monkey, human and murine stemness genes to identify the key mammalian stemness genes.
Publication Title
Transcriptional profiling of rhesus monkey embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11) could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Importantly, the increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G. We also identified a novel OCT4 downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. This small molecule-based stabilization of synthetic mRNA expression may have multiple applications for future cell-based research and therapeutics.
Publication Title
BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication.
Publication Title
Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional profiles of human CD34+ cells cultured in EPO and EST conditions.
Publication Title
Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C57BL/6J mice were 105-fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5 Mbp region on chromosome 11 encoding a cluster of three p47GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype, implicating the non-redundant role of these p47GTPases. C57BL/6J and DBA/2J exhibited a difference in IFNg dependent chlamydial control, which was reversible by Iigp2 siRNA knockdown. Microarrays of infected peritoneal lavage revealed >10 fold up regulation of neutrophil recruiting chemokines in susceptible mice and >100 fold increase in macrophage differentiation genes in resistant mice, indicating that susceptibility pattern involves stimulation of different inflammatory cell recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived lethal challenge confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Results indicate that these p47GTPases have cell autonomous effects, which results in vastly different inflammatory stimulation leading to either recovery or death.
Publication Title
The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Ovis aries
- 40 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Expression profiling of sheep born to Australian industry sires with high and low genetic merit (Estimated Breeding Values or EBVs) for eye muscle depth (EMD). Progeny (40) from six Poll Dorset sires representing well defined extremes of EBVs for Eye Muscle Depth (low EBV EMD and high EBV EMD) were selected for analysis. The six sires were Australian industry sires with three sires representative of low EBV EMD and three representing high EBV EMD.
Publication Title
An Always Correlated gene expression landscape for ovine skeletal muscle, lessons learnt from comparison with an "equivalent" bovine landscape.
Sample Metadata Fields
No sample metadata fields
View Samples