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SRP097847
Mus musculus
24 Downloadable Samples
Illumina HiSeq 4000
Description
Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. Overall design: RNA-sequencing of 12 Smarcb1-deficient mouse cranial nerves and meninges tumors
Publication Title
Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina Genome Analyzer
Description
This report not only adds a novel mechanism to the current dogma on achieving global shortening of 3''UTRs, but also unveils a novel function of the NMD pathway in establishing tissue-specific transcriptome identity Overall design: We first generated prospermatogonia-specific Upf2 conditional knockout mice (Ddx4-Cre; Upf2 fl/?, hereafter called Ddx4-KO) by crossing Ddx4-Cre13 with Upf2 floxed.
Publication Title
UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 299 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Publication Title
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation. Overall design: Total RNA was extracted from HeLa cells treated with control (CTRL), UBL5 (#57, #58, or #82), or SART1 siRNAs for 48 h and processed for RNA-Seq analysis
Publication Title
UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Cap Analysis of Gene Expression (CAGE) applied on carbon nanotubes exposed lung tissue to identify alternative promoter and enhancer usage after 24 hr of exposure in order to investigate the nature of the response observed in these mice. Overall design: C57BL/6 mice was exposed to vehicle or multi walled carbon nanotubes (MWCNT) by intratracheal installation. 5 mice was exposed to 162 ug of MWCNTs ( XNRI-7; lot05072001K28, Hadoga Chemical industry (formerly known as Mitsui) disolved in 0.9% NaCl and 10% v/v cellfree cellular broncho alveolar lavage (BAL) fluid collected from C57BL/6 mice. 6 mice was exposed to the previously decribed saline/BAL solution but without carbon nanotubes.
Publication Title
Identification of Gene Transcription Start Sites and Enhancers Responding to Pulmonary Carbon Nanotube Exposure in Vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a progenitor cells gene expression program, while priming a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdts first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.
Publication Title
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.
Sample Metadata Fields
Sex, Disease, Disease stage, Subject, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 1000
Description
Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription. Overall design: We used a siRNA approach to knock-down Atad2 and measure the resulting variations in gene expression by RNA-seq
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples