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Homo sapiens
16 Downloadable Samples
NextSeq 500
Description
Human dendritic cells were exposed to LPS, in the absence and presence of adenosine receptor 3 inhibitor Overall design: 4 donors, 4 experimental conditions. VUF concentration used was 5 µM, LPS was 500 ng/ml. Exposure times were 6 hours
Publication Title
TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A<sub>3</sub> Receptor-Mediated Signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 71 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntingtons disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation. We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics.
Publication Title
HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntingtons disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation. We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics.
Publication Title
HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 298 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version, custom CDF (huex10st)
Description
Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).
Publication Title
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.
Sample Metadata Fields
Age, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis. Overall design: mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate
Publication Title
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2000
Description
Thymic Treg cells, mature non-Treg CD4+ single positive thymocytes, peripheral (spleen) resting and activated Treg cells were sorted from Foxp3-gfp reporter (wid type, WT) mice or Foxp3 enhancer CNS3 knockout (KO, carrying the same GFP reporter) mice. Total RNA was extracted and used for RNA sequencing to assess gene expression profiles. Overall design: Two 6-8 week old littermates of male Foxp3-gfp and Foxp3?CNS3-gfp mice were used to sort Treg cells and conventional CD4+ T cells. Lymphocyte preparation and electronic sorting were performed at the same time. RNA extraction, SMART amplification, library preparation were conducted in parallel.
Publication Title
A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 525 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. 28 CEBPAdouble-mut and 13 CEBPAsingle-mut cases. CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1 mutation, white blood cell count and age. In contrast, CEBPAsingle-mut AMLs did not express a discriminating signature and could not be distinguished from wild type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance.
Publication Title
Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples
GSE18497- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomewide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (stable group), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (skewed group), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.
Publication Title
Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
Background and Purpose—Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. Methods—We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. Results—We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions—For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture. Overall design: RNA sequencing of 44 intracranial aneurysm samples (including 21 unruptured, 22 ruptured and 1 undetermined) and 16 control samples of the intracranial cortical artery
Publication Title
RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.
Sample Metadata Fields
Sex, Age, Subject
View Samples