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SRP169553
Mus musculus
17 Downloadable Samples
Illumina Genome Analyzer
Description
The RNA splicing factor SF3B1 is recurrently mutated in chronic lymphocytic leukemia (CLL), but its functional role in the pathogenesis of this disease has not been firmly established. Here, we show that conditional expression of heterozygous Sf3b1-K700E mutation in mouse B lineage cells disrupts pre-mRNA splicing, alters B-cell development and function, and induces a state of cellular senescence. B-cell restricted expression of this mutation combined with Atm deletion led to the overcoming of cellular senescence, together with enhanced genome instability and the development of clonal B220+CD5+ CLL cells in elderly mice at low penetrance. Mice with CLL-like disease were found to have amplifications of chromosomes 15 and 17. Integrated transcriptome and proteome analysis of the CLL-like cells revealed coordinated dysregulation of multiple CLL-associated cellular processes. This included an unexpected signature of deregulated B-cell receptor (BCR) signaling, which we could also identify in SF3B1-mutated CLL samples from two independent patient cohorts. Notably, human CLLs harboring SF3B1 mutations exhibited greater sensitivity and altered response kinetics to BTK kinase ibrutinib. Our genetically faithful murine model of CLL thus reveals fresh insights regarding the impact of SF3B1 mutation on CLL pathogenesis and suggests a system for identifying vulnerabilities related to this mutation that can be further exploited for the treatment of CLLs with this common mutation. Overall design: RNA-seq of B cells from WT, Sf3b1 MT, Atm MT, DM and DM-CLL mice
Publication Title
A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ERbeta attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure.
Publication Title
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of concordance in single and multi-gene genomic indices from data generated by two different laboratories (MD Anderson Cancer Center (MDA) and Jules Bordet Institute (JBI)) and on two different Affymetrix platforms (U113A and U133_Plus2).
Publication Title
Genomic index of sensitivity to endocrine therapy for breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Pressure overload (PO) leads first to cardiac hypertrophy and later to heart failure. In mice, PO leads to sex differences in cardiac morphology and function. However, early sex differences in gene regulation that precede sex differences in function have not yet been identified.
Publication Title
Sex-specific pathways in early cardiac response to pressure overload in mice.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of 80 glioblastoma specimen of patients treated within clinical trials and 4 samples of "normal" brain tissue (non-tumoral). The data was used to identify factors of resistance to a chemoradiation therapy protocol of radiotherapy and concomitant and adjuvant temozolomide (alkylating agent).
Publication Title
Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
We applied ribosome profiling and RNA sequencing to examine gene expression regulation during oncogenic cell transformation. One model involves normal mammary epithelial cells (MCF10A) containing ER-Src. Treatment of such cells with tamoxifen rapidly induces Src, thereby making it possible to kinetically follow the transition between normal and transformed cells. The other model consists of three isogenic cell lines derived from primary fibroblasts in a serial manner (Hahn et al., 1999). EH cell is immortalized by overexpression of telomerase (hTERT), and exhibits normal fibroblast morphology. EL cell expresses hTERT along with both large and small T antigens of Simian virus 40, and it displays an altered morphology but is not transformed. ELR cell expresses hTERT, T antigens, and an oncogenic derivative of Ras (H-RasV12). Overall design: Ribosome profiling and RNA sequencing in two cancer cell models
Publication Title
Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 1138 Downloadable Samples
- NextSeq 500
Description
The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq with anatomical brain registration to create a comprehensive map of the zebrafish habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ~13000 habenular cells (>4x coverage) identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a common reference atlas created a rich resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult habenula. This study provides a gene expression atlas to dissect habenular development and function and offers a general framework for the comprehensive characterization of other brain regions. Overall design: gng8-GFP zebrafish heads were dissected, dissociated and FAC sorted into 96 well plates. Single cell libraries were generated in batches of 384 cells using Smart-seq2. A total of 22 gng8-GFP fish were dissected in 3 batches and 384 cells were processed from each using Smart-seq2.
Publication Title
Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types Using Single-Cell RNA-Seq.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 52 Downloadable Samples
- Illumina HiSeq 1500
Description
In D. melanogaster males, X chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long. Although the activating Dosage Compensation Complex (DCC) associates with the chromosome and acetylates histone H4 early, many genes are not compensated. Acetylation levels on gene bodies continue to increase for several hours after gastrulation in parallel with progressive compensation. Constitutive genes are compensated earlier than developmental genes. Remarkably, later compensation correlates with longer distances to DCC binding sites. This time-space relationship suggests that DCC action on target genes requires maturation of the active chromosome compartment. Overall design: RNA-seq in 8 embryonic stages in total 54 single embryos.
Publication Title
Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARa, PPAR?, and LXRa in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARa targets contributing to gene expression changes that lead to steatosis in aged liver. Overall design: Genome-wide expression profiles (RNA-Seq) from young (3 months) and old (21 months) mouse livers
Publication Title
Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 1138 Downloadable Samples
- Illumina HiSeq 2500
Description
Spatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. Overall design: We generated single-cell RNA-seq profiles from dissociated cells from developing zebrafish embryos (late blastula stage - 50% epiboly)
Publication Title
Spatial reconstruction of single-cell gene expression data.
Sample Metadata Fields
Subject
View Samples