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GSE64603
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Little is known on the immune status in liver and blood of chronic HCV patients long after therapy-induced viral clearance. In this study, we demonstrate that 4 years after clearance, regulation of HCV-specific immunity in blood by regulatory T-cells (Treg) and the immunosuppressive cytokines IL-10 and TGF- is still ongoing. Importantly, sampling of the liver 4 years after clearance shows that intrahepatic Treg are still present in all patients, suggesting that liver T-cells remain regulated. Identifying mechanisms that regulate HCV-specific memory T-cell responses after clearance is highly relevant for the development of protective vaccines, especially in patients at high-risk of reinfection.
Publication Title
The Intrahepatic T Cell Compartment Does Not Normalize Years After Therapy-Induced Hepatitis C Virus Eradication.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study, we studied chronic HCV patients who responded to IFN-based therapy as evidenced by absence of HCV RNA at the end of treatment, and focused on two issues that have not received much attention. Firstly, we evaluated whether specific genes or gene expression patterns in blood were able to distinguish responder patients with a viral relapse from responder patients who remained virus-negative after cessation of treatment. We found that chronic HCV patients who were sustained responders and relapsers to IFN-based therapy showed comparable baseline clinical parameters and immune composition in blood. However, at baseline, the gene expression profiles of a set of 18 genes predicted treatment outcome with an accuracy of 94%. Secondly, we examined whether patients with successful therapy-induced clearance of HCV still exhibited gene expression patterns characteristic for HCV, or whether normalization of their transcriptome was observed. We observed that the relatively high expression of IFN-stimulated genes (ISG) in chronic HCV patients prior to therapy was reduced after successful IFN-based antiviral therapy (at 24 weeks follow-up). These ISG included CXCL10, OAS1, IFI6, DDX60, TRIM5 and STAT1. In addition, 1428 differentially expressed non-ISG genes were identified in paired pre- and post-treatment samples from sustained responders, which included genes involved in TGF- signaling, apoptosis, autophagy, and nucleic acid and protein metabolism. Interestingly, 1424 genes were identified with altered expression in responder patients after viral eradication in comparison to normal expression levels in healthy individuals. Additionally, aberrant expression of a subset of these genes, including IL-32, IL-16, CCND3 and RASSF1, was also observed at baseline. Our findings indicate that successful antiviral therapy of chronic HCV patients does not lead to normalization of their blood transcriptional signature. The altered transcriptional activity may reflect HCV-induced liver damage in previously infected individuals.
Publication Title
Gene expression profiling to predict and assess the consequences of therapy-induced virus eradication in chronic hepatitis C virus infection.
Sample Metadata Fields
Sex, Specimen part, Disease, Race
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
We sequenced mRNA from 12 samples extracted from mouse amygdala tissue to generate the first amygdala-specific murine transcriptome for germ-free mice (GF), conventionally raised controls (CON) and germ-free mice that have been colonized with normal microbiota from postnatal day 21 (exGF). Overall design: Equal amounts of RNA from two to three animals were pooled to yield 4 samples per group (CON, GF, and exGF). Pairwise comparisons for CONvsGF, CONvsexGF, GFvsexGF were performed using DESeq2.
Publication Title
Microbes & neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer.
Publication Title
Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study is part of a larger multidisciplinary study entitled A dormant sub-population expressing interleukin-1 receptor characterises anti-estrogen resistant ALDH+ breast cancer stem cells.
Publication Title
Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH<sup>+</sup> Breast Cancer Stem Cells.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bacterial infections cause exaserbations in COPD. Study conducted to asses the effect of Nemiralisib, a PI3Kdelta inhibitor, on S. pneumoniae infected mice
Publication Title
PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
Description
Organoid technologies provide an accessible system in which to examine the generation, self-organization,and 3-dimensional cellular interactions during development of the human cerebral cortex. However, oligodendrocytes, the myelinating glia of the central nervous system and third major neural cell type, are conspicuously absent from current protocols. Here we reproducibly generate human oligodendrocytes and myelin in pluripotent stem cell-derived cortical spheroids. Transcriptional and immunohistochemical analysis of the spheroids demonstrates molecular features consistent with maturing human oligodendrocytes within 14 weeks of culture, including expression of MyRF, PLP1, and MBP proteins. Histological analysis by electron microscopy shows initial wrapping of human neuronal axons with myelin by 20 weeks and maturation to compact myelin by 30 weeks in culture. Treatment of spheroids with previously identified promyelinating drugs enhances the rate and extent of human oligodendrocyte generation and myelination. Furthermore, generation of spheroids from patients with a severe genetic myelin disorder, Pelizaeus-Merzbacher disease, demonstrates the ability to recapitulate human disease phenotypes, which were in turn improved with both pharmacologic and CRISPR-based approaches. Collectively, these 3-dimensional, multi-lineage cortical spheroids provide a versatile platform to observe and perturb the complex cellular interactions that occur during developmental myelination of the brain and offer new opportunities for disease modeling and therapeutic development in human tissue. Overall design: RNAseq profiles comparing neuro-cortical spheroids and oligo-cortical spheroids
Publication Title
Induction of myelinating oligodendrocytes in human cortical spheroids.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- NextSeq 500
Description
Fine control of macrophage activation is required to prevent inflammatory disease, particularly at barrier sites such as the lung. However, the dominant mechanisms that regulate pulmonary MFs during inflammation are currently poorly understood. Here we show that airway MFs are substantially less able to respond to the canonical type-2 cytokine IL-4, which underpins allergic disease and parasite worm infections, than lung tissue or peritoneal cavity MFs. We reveal that MF hypo-responsiveness to IL-4 is dictated by the lung environment, though independent of the host microbiota or the prominent lung extracellular matrix components surfactant protein D and mucin 5b. Rather, compared to cavity MFs, airway MFs display severely dysregulated metabolism. Strikingly, upon removal from the lung, alveolar MFs regain IL-4 responsiveness in a process dependent upon glycolysis. Thus, we propose that impaired glycolysis within the pulmonary niche is a central determinant for regulation of MF responsiveness during type-2 inflammation. Overall design: The 13 analysed samples belong to 6 different groups, each group consisted of 2 or 3 samples. The groups consist of 3 separate macrophage populations, from either control or IL-4 complex treated mice. Each individual sample was generated from 3-5 pooled biological replicate mice.
Publication Title
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.
Sample Metadata Fields
Treatment, 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- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Non-overlapping progesterone receptor cistromes contribute to cell-specific transcriptional outcomes.
Sample Metadata Fields
Specimen part, Cell line
View Samples