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SRP155027
Homo sapiens
5 Downloadable Samples
Illumina HiSeq 2000
Description
EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo. Overall design: The NSCLC cell line PC9 was made tolerant to gefitinib over 6-days. Replicates were performed at a minimum of duplicates. EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo.
Publication Title
Increased Synthesis of MCL-1 Protein Underlies Initial Survival of <i>EGFR</i>-Mutant Lung Cancer to EGFR Inhibitors and Provides a Novel Drug Target.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.
Publication Title
Recurrent epimutation of SDHC in gastrointestinal stromal tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to identify ion channels, specifically transient receptor potential cation channel A (trpA1) channels, that were highly expressed and enriched in nociceptive sensory neurons of Drosophila larvae. In class IV da sensory neurons, we find that TrpA1 is the most highly expressed trpA1 channel of the 14 trpA1 channels in Drosophila, and that its expression is highly enriched when compared to the whole animal transcriptome. Overall design: Four biological replicates of 100 Drosophila melanogaster larval class IV dendritic arborization sensory neurons and five biological replicates of whole Drosophila melanogaster larvae were profiled by mRNA-Seq
Publication Title
TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize gene response in RPE65-/- mouse model of Lebers congenital amaurosis during progression of the disease, we analyzed differential gene expression in retinae early in the development of the disease, namely before and at the onset of photoreceptor cell death in knock-out mice of 2, 4 and 6 months of age.
Publication Title
Biological characterization of gene response in Rpe65-/- mouse model of Leber's congenital amaurosis during progression of the disease.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to examine changes in gene expression in multiple myeloma cell lines following treatment with arsenic trioxide and darinaparsin
Publication Title
Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Meiotic recombination is initiated by the Spo11 endonuclease, which directs DNA double strand breaks at discrete regions in the genome coined hotspots. Here we report the profiles and dynamics of histone modifications at the cores of mouse recombination hotspots in early meiotic prophase. To define the spectrum of possible regulators of histone methylation and acetylation at all stages of meiosis I, expression analyses of histone acetylases/deacetylases (HATs/HDACs) and and HMTs/HDMTs genes when comparing those expressed in spermatogonia, pre-leptotene and leptotene/zygotene versus pachytene meiotic stages.
Publication Title
Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TGZ is an agonist of the nuclear receptor PPARgamma. This synthetic compound displays anticancer effects on breast cancer cells but some of them are PPARgamma independent. Delta-2-TGZ (delta-2-troglotazone) is a PPARgamma inactive TGZ derivative possessing a double bond adjoining the thiazolidinedione ring. This compound still displays anticancer efefcts. It is an interesting tool to study the PPARgamma-independent mechanisms.
Publication Title
Pro-apoptotic effect of Δ2-TGZ in "claudin-1-low" triple-negative breast cancer cells: involvement of claudin-1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 4000
Description
Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5 year-old child with severe pulmonary influenza at 2 years. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not interferon-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-a2b. The transcriptome induced by IFN-a2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of interferon-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus, and respiratory syncytial virus. These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV. Overall design: Total of 72 samples, 38 samples from primary fibroblasts and 34 samples from EBV-transformed B cells, were analyzed using paired-end RNA sequence data. Out of 38 samples from primary fibroblasts, 3 control samples are paired with no stimulation vs IFNa2b stimulation. Out of 34 samples from B-cells, 3 control samples are paired with no stimuliion vs IFNa2b stimulation. In addition to healthy control subjects, patients with AR complete STAT1 (STAT1 -/-) or STAT2 (STAT2 -/-) deficiency were analyzed for comparison.
Publication Title
Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 67 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
We present single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11. Our study reveals the transcriptional dynamics occuring during endothelial to hematopoietic transition, the process responsible for the production of hematopoietic stem cells. Overall design: single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11
Publication Title
Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples