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SRP024394
Drosophila melanogaster
30 Downloadable Samples
Illumina HiSeq 2000
Description
We found that the midgut shows striking regional differentiation along its anterior-posterior axis. Ten distinct subregions differ in cell morphology, gene expression and aspects of Notch signaling. RNA from isolated regions that was analyzed by RNAseq revealed spatially regulated expression of hundreds of enzymes and other genes with likely tissue functions. Overall design: 10 midgut segments comprising from 1-3 subregions x 3 replicates from each segment = 30 samples
Publication Title
Physiological and stem cell compartmentalization within the Drosophila midgut.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
Affymetrix Murine 11K SubA Array (mu11ksuba)
Description
Mammalian lung development is a complex morphogenetic process, which initiates near mid-gestation and continues through early postnatal life. The lung arises as two lateral buds that emerge from the ventral foregut endoderm at ~ 9 days after fertilization (in mouse) and undergo numerous rounds of dichotomous branching to form the bronchial tree. This stage of development is referred to as the pseudoglandular phase, histologically characterized by loose mesenchyme surrounding undifferentiated epithelial tubes.
Publication Title
Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 4000, Illumina HiSeq 2000
Description
Resistance to proteasome inhibitors (PIs) is a ubiquitous clinical concern in multiple myeloma (MM). We proposed that signaling-level responses after PI would reveal new means to enhance efficacy. Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on spliceosome components. Spliceosome modulation was invisible to RNA or protein abundance alone. Transcriptome analysis demonstrated broad-scale intron retention suggestive of PI-specific splicing interference. Direct spliceosome inhibition synergized with carfilzomib and showed potent anti-myeloma activity. Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerabilityin myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma. Overall design: We examine 1) gene expression of MM cells in response to PI and 2)alternative splicing in response to PI and comparator chemotherapeutic compound. We further investigate splice factor mechanism in MM cells, by examining alternative splicing in MM with overexpression of wild type and mutant splice factor, SRSF1
Publication Title
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma.
Sample Metadata Fields
Cell line, Subject, Compound, Time
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiling of newborn lung tissue revealed few changes in compound FGFR3/FGFR4 deficient mice, consistent with their normal lung morphology at birth, suggesting the sequence of events leading to the phenotype initiates after birth in this model.
Publication Title
Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Rationale: Maternal immune responses can promote allergy development in offspring. Pilot data show that neonates of mother mice exposed during pregnancy to air pollution particles have increased allergic susceptibility. Objective: We investigated whether inflammatory response to titanium dioxide (TiO2) particles earlier considered immunologically inert is enhanced during pregnancy. Methods: Pregnant BALB/c mice (or non-pregnant controls) received particle suspensions intranasally at day 14 of pregnancy. Lung inflammatory responses were evaluated 19 and 48 h after exposure. Results: Pregnant mice showed robust and persistent acute inflammatory responses after exposure to TiO2, while non-pregnant females had the expected minimal responses. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (but not PBS) developed increased susceptibility to allergens. Conclusion: Pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles.
Publication Title
Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Transcriptome analysis of two Ph+ acute lymphoblastic leukemia cell lines after doxycycline induced silencing of MYB.
Publication Title
Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph<sup>+</sup> Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with complex pathological features and largely unknown etiologies. Identification and validation of biomarkers for this disease could facilitate earlier diagnosis, appreciation of disease subtypes and/or determination of response to therapeutic intervention. To identify gene expression markers for COPD, we performed genome-wide expression profiling of lung tissue from 56 subjects using the Affymetrix U133 Plus 2.0 array. Lung function measurements from these subjects ranged from normal, un-obstructed to severely obstructed. Analysis of differential expression between cases (FEV1<70%, FEV1/FVC<0.7) and controls (FEV1>80%, FEV1/FVC>0.7) identified a set of 65 probe sets representing discrete markers associated with COPD. Correlation of gene expression with quantitative measures of airflow obstruction (FEV1 or FEV1/FVC) identified a set of 220 probe sets. A total of 31 probe sets were identified that showed evidence of significant correlation with quantitative traits and differential expression between cases and controls.
Publication Title
Molecular biomarkers for quantitative and discrete COPD phenotypes.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs), and further down to sub-TAD loop domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here we present a novel parameter-free algorithm (CaTCH) that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation which is a simple and biologically relevant property. By applying CaTCH to published Hi-C datasets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal enrichment of CTCF at boundaries, and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that TADs also maximize the likelihood that genes in a domain are co-regulated during differentiation. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the scale of TADs. Our analysis thus suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the genomic position of regulatory sequences. Overall design: The hybrid mouse ESC line F1-21.6 (129Sv-Cast/EiJ), previously described in (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), and 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared by Trizol extraction from the mouse ESC line, and for one NPC clone derived from it. Two biological replicates were collected for ESCs and NPCs. After ribosomal RNA depletion with Ribo-Zero (Illumina), RNA-seq libraries were prepared using ScriptSeq v2 kit (Illumina) following the manufacturer’s instructions. Libraries were prepared in two technical replicates per biological replicate. 50 bp single-end sequencing was performed on Illumina HiSeq 2000 instruments according to manufacturer’s instructions.
Publication Title
Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients. Overall design: Single-end 50 bp RNA-seq of MM.1S myeloma cell line either grown alone in monoculture, MM.1S isolated after 24 hr co-culture with immortalized HS5 bone marrow stromal cells, or HS5 bone marrow stromal cells grown alone
Publication Title
Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
HCT116 colon carcinoma cells invade more the basement membrane when carcinoma-associated fibroblasts (CAFs) are present. In order to identify if CAFs induce an invasive phenotype to HCT116 cells, and therefore regulate genes expression related to invasion, we compared gene expression of HCT116 cells cultured alone or in the presence of CAFs.
Publication Title
Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane.
Sample Metadata Fields
Disease, Cell line
View Samples