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Mus musculus
31 Downloadable Samples
Illumina HiSeq 2500
Description
DNA methylation and other repressive epigenetic marks are erased genome-wide in mammalian primordial germ cells (PGCs), the early embryo and in naïve embryonic stem cells (ESCs). This is a critical phase for transposon element (TE) defense since presumably alternative pathways need to be employed to limit their activity. It has been reported that pervasive transcription is enriched for TEs in ESCs in comparison to somatic cells. Here we test the hypothesis that pervasive transcription overlapping TEs forms a sensor for loss of their transcriptional repression. Overlapping sense and antisense transcription is found in TEs, and the increase of sense transcription induced by acute deletion of DNMT1 leads to the emergence of small RNAs. These small RNAs are loaded into ARGONAUTE 2 suggesting an endosiRNA mechanism for transposon silencing. Indeed, deletion of DICER reveals this mechanism to be important for silencing of certain transposon classes, while others are additionally repressed by deposition of repressive histone marks. Our observations suggest that pervasive transcription overlapping with TEs resulting in endosiRNAs is a transposon sensor that restrains their activity during epigenetic reprogramming in the germline. Overall design: Total RNA-seq libraires (2 biological replicates of 16 samples, 1 biological replicate of 1 sample)
Publication Title
An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 140 Downloadable Samples
- NextSeq 550
Description
DNA is strictly compartmentalised within the nucleus to prevent autoimmunity despite this cGAS, a cytosolic sensor of dsDNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localises to micronuclei arising from genome instability in a model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. These micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by their own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS binds to and is activated by chromatin and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA-damage are cell-cycle dependent. Furthermore, by combining live-cell laser microdissection with single cell transcriptomics, we establish that induction of interferon stimulated gene expression occurs in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, cGAS recognition of micronuclei may act as a cell-intrinsic immune surveillance mechanism detecting a range of neoplasia-inducing processes. Overall design: RNA-seq of 35 individual mouse embryonic fibroblasts 48 h after 1 Gy irradiation: 21 test (with micronuclei) and 14 controls (without micronuclei).
Publication Title
cGAS surveillance of micronuclei links genome instability to innate immunity.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
PIWI interacting RNAs (piRNAs) provide defense against transposable element (TE) expansion in the germline of metazoans. piRNAs are processed from the transcripts encoded by specialized heterochromatic clusters enriched in damaged copies of transposons. How these regions are recognized as a source of piRNAs is still elusive. The aim of this study is to determine how transgenes that contain a fragment of the LINE-like I transposon lead to an acquired TE resistance in Drosophila. We show that such transgenes, being inserted in unique euchromatic regions which normally do not produce small RNAs, become de novo bidirectional piRNA clusters that silence I-element activity in the germline. Strikingly, small RNAs of both polarities are generated from the entire transgene and flanking genomic sequences — not only from the transposon fragment. Chromatin immunoprecipitation analysis shows that in ovaries the trimethylated histone 3 lysine 9 (H3K9me3) mark associates with transgenes producing piRNAs. We show that transgene-derived hsp70 piRNAs stimulate in trans cleavage of cognate endogenous transcripts with subsequent processing of the non-homologous parts of these transcripts into piRNAs. Overall design: The fractions of small RNAs (19-29 nt) from ovaries of wild type and 11 transgenic lines of Drosophila melanogaster were sequenced using Illumina HiSeq 2000.
Publication Title
De novo piRNA cluster formation in the Drosophila germ line triggered by transgenes containing a transcribed transposon fragment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 71 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Publication Title
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Publication Title
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling of normal hematopoietic cell subpopulations
Publication Title
Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
Sample Metadata Fields
Specimen part
View Samples
GSE13124- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional expression data for bioactive small molecules for mechanism identification.
Publication Title
Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
M21 or M21L cells were grown either in a 2-dimensional culture (on plastic) or in a 3-dimensional-collagen model.
Publication Title
Protein kinase Cα (PKCα) regulates p53 localization and melanoma cell survival downstream of integrin αv in three-dimensional collagen and in vivo.
Sample Metadata Fields
Cell line
View Samples GSE16709- Homo sapiens
- 39 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples