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GSE18607
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice.
Publication Title
Type-I IFN signaling suppresses an excessive IFN-gamma response and thus prevents lung damage and chronic inflammation during Pneumocystis (PC) clearance in CD4 T cell-competent mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency or developmentally related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.
Publication Title
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The S1 and S3 erythroid developmental subsets were isolated using flow cytometry and the cell surface markers CD71 and Ter119 as described by Pop et. al. 2010 (PMID: 20877475)
Publication Title
Global DNA demethylation during mouse erythropoiesis in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene Expression profiling of HSCs isolated at different stages of ontogeny to address correlation between gene expression and changes in DNA methylation
Publication Title
Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Resistance formation is one of the major hurdles in cancer therapy. Metronomic anti-angiogenic treatment of xenografted prostate cancer tumors in SCID mice with cyclophosphamide (CPA) results in the appearance of resistant tumors. To investigate the complex molecular changes occurring during resistance formation, we performed a comprehensive gene expression analysis of the resistant tumors in vivo. We observed a multitude of differentially expressed genes, e.g., PASD1, ANXA3, NTS or PLAT, when comparing resistant to in vivo passaged tumor samples. Furthermore, tumor cells from in vivo and in vitro conditions showed a significant difference in target gene expression. We assigned the differentially expressed genes to functional pathways like axon guidance, steroid biosynthesis and complement and coagulation cascades. Most of the genes were involved in anti-coagulation, indicating its possible importance. Upregulation of anti-coagulatory ANXA3 and PLAT and downregulation of PLAT inhibitor SERPINA were validated by qPCR. In contrast, coagulation factor F3 was upregulated, accompanied by the expression of an altered gene product. These findings give insights into the resistance mechanisms of metronomical CPA treatment suggesting an important role of anti-coagulation in resistance formation.
Publication Title
A Comprehensive Gene Expression Analysis of Resistance Formation upon Metronomic Cyclophosphamide Therapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 68 Downloadable Samples
Illumina HiSeq 2500
Description
Concerted efforts over past decades have established a thorough understanding of the canonical somatic DNA methylation landscape as well as its systematic misregulation across most human cancers. However, the underlying mechanism that directs this genome-scale transformation remains elusive, with no clear model for its acquisition or understanding of its potential developmental utility. Here we present base pair resolution analysis of global remethylation from the hypomethylated state of the preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions: while the proximal epiblast establishes a canonical CpG-density dependent pattern found in somatic cells, the extraembryonic epigenome becomes substantially more mosaic. Moreover, this alternate pattern includes specific de novo methylation of hundreds of CpG island promoter containing genes that function in early embryonic development and are orthologously methylated across an extensive cohort of human cancers. From these data, we propose a model where the evolutionary innovation of extraembryonic tissues in eutherian mammals required cooption of DNA methylation-based suppression as an alternate pathway to the embryonically utilized Polycomb group proteins, which otherwise coordinate germ layer formation in response to extraembryonic cues at the onset of gastrulation. Moreover, we establish that this decision is made deterministically downstream of the promiscuously utilized, and frequently oncogenic, FGF signaling pathway and utilizes a novel combination of epigenetic cofactors. Recruitment of this silencing mechanism to developmental genes during cancer therefore reflects the misappropriation of an innate regulatory pathway that may be spontaneously sampled as an alternate epigenetic landscape within somatic cells. Overall design: Comparison of gene expression patterns in Extraembryonic Ectoderm and cancer
Publication Title
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Chronic hepatitis C virus (HCV) infection is now routinely treated with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents. Changes in hepatic and peripheral innate and adaptive immune function during DAA therapy associate with achieving a sustained virologic response (SVR). The present study explored the impact of cirrhosis on host endogenous interferon pathways during DAA therapy. mRNA and micro-RNA (miRNA) expression profiling was performed on paired pre- and end-of-treatment (EOT) liver biopsies from subjects treated with a 2 DAA regimen (sofosbuvir/ledipasvir [SOF/LDV]) for 12 weeks (n=4, 3 with cirrhosis) or a 3 DAA regimen (SOF/LDV with GS-9669 or GS-9451) for 6 weeks (n=6, 0 with cirrhosis). Nine of ten subjects achieved SVR, with one relapse in the GS-9669 treatment arm (ISHAK fibrosis 4). Hepatic interferon-stimulated gene expression was down-regulated in the liver of all subjects, with no observable impact of cirrhosis or duration of treatment. Hepatic down-regulation of all type-III IFNs was observed (IFNL1, IFNL2, IFNL3, IFNL4-G), while IFNA2 expression, undetectable in all subjects pre-treatment, was detected in 3 of 9 subjects at EOT (all 3 achieved SVR). Only the subject who relapsed had detectable IFNL4-G expression in EOT liver. No change in IFNB1, IFNG, or IFNA5 expression was observed, and expression of other type-I IFNs (IFNA1, IFNA4, IFNA5, IFNA6, IFNA8, IFNA16, IFNA17) was not detected pre- or post-treatment. While expression of multiple miRNAs changed in liver tissue over the course of treatment, most miRNAs previously associated with HCV replication, innate interferon signaling, and hepatic fibrosis did not change significantly. Conclusions: Changes in the host IFN-response during DAA therapy associate with favorable treatment outcome regardless of composition and duration of therapy or extent of hepatic fibrosis.
Publication Title
Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies support its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation have not been worked out in detail. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. Except for global demethylation in erythrocytes, observed DNA methylation changes were locus-specific and relatively modest in size. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided highly complementary information, and combining the two enabled us to infer the blood lineage hierarchy directly from genomic data. In summary, our dataset and analysis demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the distribution of DNA methylation across the mouse genome.
Publication Title
DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent studies demonstrated that tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We established glioblastoma stem-like (GS-) cell cultures from 9 different glioblastomas, 8 of which generated stably expandable cell lines. Analyzing GS-cell cultures, we discovered two clearly discernable phenotypes.
Publication Title
Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria.
Sample Metadata Fields
No sample metadata fields
View Samples