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SRP048701
Homo sapiens
16 Downloadable Samples
IlluminaHiSeq2000
Description
KCL-22 is a chronic myeloid leukemia (CML) cell line derived from a patient in blast crisis phase and harbors the BCR-ABL translocation. The catalytic (ATP-competitive) BCR-ABL inhibitors imatinib and nilotinib have dramatically improved CML patient outcome, but the development of resistance remains a clinical challenge. The recent identification of allosteric BCR-ABL inhibitors, such as GNF-2, which target the enzyme by binding to the myristoyl pocket rather than catalytic site of ABL1, may provide a strategy to broadly overcome resistance to the class of ABL1 ATP competitive inhibitors. We therefore wanted to use the ClonTracer barcoding system to compare the clonal responses of KCL-22 to imatinib, nilotinib and GNF-2. RNA-seq was employed to characterize genetic alterations and gene expression signatures in the pooled cell populations resistant to BCR-ABL inhibitors as well as single clones showing differential response to the three inhibitors. Overall design: mRNA profiling of the subpopulations and single clones of human CML cell line KCL-22 that contribute to BCR-ABL inhibitor resistance
Publication Title
Studying clonal dynamics in response to cancer therapy using high-complexity barcoding.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
The non-small cell lung cancer (NSCLC) cell line HCC827 harbors an activating EGFR mutation (exon 19 deletion) that confers sensitivity to the FDA-approved EGFR inhibitor erlotinib. By applying the ClonTracer barcoding system, we were able to show the presence of pre-existing sub-populations in HCC827 that contribute to erlotinib resistance. Prior studies implicated that MET amplification confers resistance to erlotinib in this cell line. Therefore we examined the effects of the c-Met inhibitor crizotinib on the barcoded HCC827 population when treated either sequentially or simultaneously with both inhibitors. Despite the significant reduction in barcode complexity, the erlotinib/crizotinib combination treatment failed to eradicate all of the resistant clones implying the presence of an erlotinib/crizotinib dual resistant subpopulation. We performed transcriptome profiling (RNA-seq) to elucidate the potential resistance mechanisms of the dual resistant subpopulation in comparison to vehicle-treated or single agent erlotinib-resistant HCC827 cell populations as controls. Overall design: mRNA profiling of the subpopulations of human NSCLC cell line HCC827 that contribute to EGFR inhibitor erlotinib and MET inhibitor crizotinib resistance
Publication Title
Studying clonal dynamics in response to cancer therapy using high-complexity barcoding.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 34 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To examine irreversible changes in the developing brain following seizures, juvenile inbred mice were intraperitoneally injected with kainate and nicotine.
Publication Title
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Asthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity. We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors. RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control. Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads. Overall design: Transcriptome profiles obtained via RNA-Seq for airway smooth muscle cells from 9 fatal asthma and 8 non-asthma donors treated with budesonide (100nM for 24h) or vehicle control were compared
Publication Title
Airway Smooth Muscle-Specific Transcriptomic Signatures of Glucocorticoid Exposure.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Mus musculus, Rattus norvegicus
- 100 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
-chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of multi-organ tumors in mouse and rat cancer bioassays. A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12.8 ppm while a small, but not statistically significant, increase was observed in female rats only at the highest exposure concentration of 80 ppm. The metabolism of chloroprene results in the generation of reactive epoxides and the rate of overall chloroprene metabolism is highly species dependent. To identify potential key events in the mode-of-action of chloroprene lung tumorigenesis, dose response and time course gene expression microarray measurements were made in the lungs of female mice and female rats. The gene expression changes were analyzed using both a traditional analysis of variance approach followed by pathway enrichment analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross-species differences in tumor incidence and transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day. The closer correspondence of the transcriptional changes with the tumor response are likely due to their reflection of the overall balance between metabolic activation and detoxication reactions whereas the current tissue dose surrogate reflects only oxidative metabolism.
Publication Title
Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Our previous studies have revealed that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 g/kg) at gestational day (GD) 15 reduces the pituitary synthesis of luteinizing hormone (LH) during late fetal and early postnatal period, leading to imprinting of defects in sexual behaviors at adulthood. However, it remains obscure how the attenuation of pituitary LH links to sexual immaturity. To address this issue, we firstly performed a DNA microarray analysis to identify the gene(s) responsible for dioxin-induced sexual immaturity, using the pituitary and hypothalamus of male pups, at the age of postnatal day (PND)70, born from TCDD-treated dams. Among the reduced genes, we focused on gonadotropin-releasing hormone (GnRH) in the hypothalamus, because of its role in sexual behaviors suggested so far. The present study strongly suggests that maternal exposure to TCDD fixes the status of the lowered expression of GnRH in the offspring by reducing steroidogenesis at perinatal stage, and this is the mechanism for the imprinting of defects in sexual behaviors at adulthood.
Publication Title
Maternal exposure to dioxin imprints sexual immaturity of the pups through fixing the status of the reduced expression of hypothalamic gonadotropin-releasing hormone.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 8 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
This study demonstrates simulated microgravity effects on E. coli K 12 MG1655 when grown on LB medium supplemented with glycerol. The results imply that E. coli readily reprograms itself to combat the multiple stresses imposed due to microgravity. Under these conditions it survives by upregulating oxidative stress protecting genes and simultaneously down regulating the membrane transporters and synthases to maintain cell homeostasis.
Publication Title
Effect of simulated microgravity on E. coli K12 MG1655 growth and gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Altered gene expression in the sphingosine 1-phosphate receptor 2 (S1P2)-deficient or sphingosine 1-phosphate receptor 3 (S1P3)-deficient brain.
Publication Title
Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Appropriate bone mass is maintained by the actions of the main cells in the bone, osteoclasts and osteoblasts. The Stat3 transcription factor is known to have an effect on maintaining bone mass, but it is not known whether its key actions are in osteoblasts, osteoclasts, or both. Preliminary data indicated that Stat3 plays a role in osteoclast differentiation, but the mechanisms of this role are not yet understood.
Publication Title
The loss of STAT3 in mature osteoclasts has detrimental effects on bone structure.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina HiSeq 2000
Description
Rationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for primary human airway smooth muscle cell lines from fatal asthma or control donors that were treated with vitamin D, albuterol, or were left untreated.
Publication Title
Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.
Sample Metadata Fields
No sample metadata fields
View Samples