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GSE58268
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
Publication Title
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
Publication Title
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Sample Metadata Fields
Specimen part
View Samples- Ovis aries
- 8 Downloadable Samples
- Ovine Gene 1.1 ST Array (ovigene10st)
Description
study investigating the initiation of systemic inflammatory signaling in fetuses exposed to TLR-4 agonist lipopolysaccharides from E.coli
Publication Title
Outside-in? Acute fetal systemic inflammation in very preterm chronically catheterized sheep fetuses is not driven by cells in the fetal blood.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Beta-arrestin 1 (ARRB1) has been implicated in transcriptional regulation as part of protein complexes bound to chromatin. Here we investigate its effect on transcription and its potential impact on prostate cancer. We report the first genome-wide mapping of chromatin binding for ARRB1 and combine it with expression array data to define its transcriptome. We identify Hypoxia Inducible Factor 1A (HIF1A) as a nuclear binding partner that recruits ARRB1 to promoter regions of HIF1A targets. We show that ARRB1 modulates HIF1A-dependent transcription and promotes a shift in cellular metabolism from oxidative phosphorylation to aerobic glycolysis. In addition, we show that ARRB1 plays an important role in neoplastic transformation, cell growth and resistance to hypoxic stress. This is the first example of an endocytic adaptor protein regulating metabolic pathways and implicates ARRB1 as a tumour promoter.
Publication Title
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Macaca fascicularis
- 222 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Relatively little is understood about the dynamics of global hostpathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our Q:2 results are unique in providing a comprehensive understanding of the hostpathogen interactome during mucosal infection by a bacterial pathogen.
Publication Title
Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2500
Description
Myc expression cooperates with Rb1 and Trp53 loss in mouse lungs to generate rapid, aggressive, highly metastatic and neuroendocrine-low tumors that are similar to human variant subset of SCLC with high NEUROD1 expression. Targeted drug screening reveals that mouse and human MYC-driven SCLC are vulnerable to Aurora kinase inhibition in combination with chemotherapy in vivo. Overall design: Tumor formation is induced by infecting the conditional Rb1 fl/fl; Trp53 fl/fl, LSL-Myc (T58A) and Rb1 fl/fl; Trp53 fl/fl, p130 fl/fl GEMMs with adenoviruses with Cgrp promoter driving Cre recombinase. The tumors were macro-dissected from lungs. RNA was extracted from fresh or flash frozen tumors and subjected to single end RNA sequencing.
Publication Title
MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- NextSeq 500
Description
Liver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence underlies this regenerative failure. In human acute liver disease, and murine models, p21-dependent hepatocellular senescence was proportionate to disease severity and was associated with impaired regeneration. In an acetaminophen injury model a transcriptional signature associated with the induction of paracrine senescence is observed within twenty four hours, and is followed by one of impaired proliferation. In genetic models of hepatocyte injury and senescence we observed transmission of senescence to local uninjured hepatocytes. Spread of senescence depended upon macrophage derived TGFß1 ligand. In acetaminophen poisoning inhibition of TGFß receptor 1 (TGFßR1) improved survival. TGFßR1 inhibition reduced senescence and enhanced liver regeneration even when delivered after the current therapeutic window. This mechanism, in which injury induced senescence impairs regeneration, is an attractive therapeutic target for acute liver failure. Overall design: RNA-seq analysis was performed on a total of 24 samples extracted from murine liver, post hepatic injury induced by acetaminophen administration. Transcriptional profiles were from replicate samples generated at defined timepoints - 12, 24, 36, 48 and 72 hours post injury. Replicate samples were generated from 4 individual animals sacrificed at each timepoint, and compared to a control cohort of 4 animals not subjected to acetaminophen treatment.
Publication Title
TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples