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GSE78227
Drosophila melanogaster
5 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
During sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Publication Title
Drosophila maleless gene counteracts X global aneuploid effects in males.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Organization of the genome in 3D nuclear-space is known to play a crucial role in regulation of gene expression. However, the chromatin architecture that impinges on the B cell-fate choice of multi-potent progenitors remains unclear. By employing in situ Hi-C, we have identified distinct sets of genomic loci that undergo a developmental switch between permissive and repressive compartments during B-cell fate commitment. Intriguingly, we show that topologically associating domains (TADs) represent co-regulated subunits of chromatin and display considerable structural alterations as a result of changes in the cis-regulatory interaction landscape. The extensive rewiring of cis-regulatory interactions is closely associated with differential gene expression programs. Further, we demonstrate the regulatory role of Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Together, our studies reveal that alterations in promoter and cis-regulatory interactions underlie changes in higher-order chromatin architecture, which in turn determines cell-identity and cell-type specific gene expression patterns.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 384 Downloadable Samples
NextSeq 500
Description
Immune checkpoint blockade has shown tremendous anti-tumor potential in the clinic. However, these therapies are only effective in a subset of patients, so identification of additional immunomodulatory molecules that enhance the anti-tumor activity of these treatments may expand their clinical utility. In particular, identifying small molecules that complement existing immunotherapies has been relatively unexplored, so we performed a small molecule screen to identify compounds that can enhance co-inhibitory molecule blockade, to improve the anti-tumor adaptive immune response. Our unbiased screen identified inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6), including the FDA-approved palbociclib, as a class of small molecule compounds that exhibited significant immunostimulatory activity in vitro. In accordance with our in vitro finding of enhanced NFAT signaling, single-cell RNA-sequencing confirmed that in vivo exposure to CDK4/6 inhibitors enhanced NFAT signaling in tumor infiltrating T cells. Moreover, our results revealed that CDK4/6 inhibition up-regulated activation molecules and down-regulated suppressive molecules in these cells. CDK4/6 inhibition also increased the number of T cells with activated TCR (T cell receptor) signaling, as well as factors that are important for signal transduction downstream of TCR signaling. In summary, the impact of CDK4/6i on cell cycle progression and T cell proliferation are balanced favorably towards increased T cell recruitment and enhanced effector cell function, mediated in part by activation of the NFAT family of transcription factors. Further, our results demonstrate that CDK4/6i enhances PD-1 blockade through increased T-cell effector function and inhibition of immune suppressive cytokine production. While prolonged CDK4/6i treatment could be immunosuppressive due to adverse effects on lymphocyte proliferation, properly timed/sequenced CDK4/6i may potentiate the clinical impact of anti-PD-1/PD-L1 antibodies. As palbociclib is FDA-approved and multiple other CDK4/6 inhibitors are in clinical trials, we expect that this hypothesis will undergo rapid testing in humans. Overall design: Single-cell comparison of control and CDK4/6 inhibitor treated tumor infiltrating T cells
Publication Title
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Neutrophils are short-lived innate immune cells. Upon encountering appropriate stimuli, neutrophils generate and release neutrophil extracellular traps (NETs), primarily via NADPH oxidase (Nox)-dependent (~2 hours) or Nox-independent NETosis (~15-60 minutes). Ironically, DNA transcription in dying neutrophils remains an enigma. We hypothesized that transcriptional activation, regulated by NETosis-specific kinases, is important to drive the chromatin decondensation necessary for NETosis. For the first time, we show here that (i) the degree of NETosis corresponds to the degree of genome-wide transcription; (ii) kinase-specific transcriptional activation reflects transcriptional firing during different types of NETosis; and (iii) Transcriptomics suggests that NETosis could differentially regulate inflammation. Therefore, we propose that the initial steps of transcriptional firing, but neither transcription per se help to drive NETosis.
Publication Title
Transcriptional firing helps to drive NETosis.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus, Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Changes in gene expression profile of intestinal (ILEUM) Tumors from APCmin/+/VP16LXRa vs APCmin/+/VP16. The hypothesis tested in the present study was that LXRa overexpression influence cancer growth modulating lipid metabolism in cancer cells. Results provide the information that LXRa induces genes encoding proteins able to regulate cholesterol efflux.
Publication Title
Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 26 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared gene expression in the Drosophila fat body on control and high-sugar diets in order to gain insight into the role of this organ during caloric overload. Differential expression analysis revealed changes in gene expression suggestive of a role for CoA metabolism in the ability to tolerate high-sugar feeding. This led us to perform biochemical and mutant studies supporting a model where CoA is limiting in the face of caloric overload. Overall design: Wild-type Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
CoA protects against the deleterious effects of caloric overload in Drosophila.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although most of the oncogenic phenotypes of PTEN loss have been attributed to AKT activation, AKT alone is not sufficient to induce all of the biological activities associated with PTEN inactivation. We searched for additional PTEN-regulated pathways through gene set enrichment analysis (GSEA) and found that PTEN inactivation causes an enrichment of genes associated with JNK activation. Biochemically, PTEN-null cells exhibit higher JNK activity, and genetic studies demonstrate that JNK functions parallel to and independently of AKT. Furthermore, PTEN deficiency sensitizes cells to JNK inhibition. We also found that negative feedback regulation of PI3K was impaired in PTEN-null cells. These findings implicate JNK in PI3K-driven cancers and demonstrate the utility of GSEA to identify functional pathways using genetically defined systems.
Publication Title
Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Forced sustained swimming exercise at optimal speed enhances growth in many fish species, particularly through hypertrophy of the white skeletal muscle. The exact mechanism of this effect has not been resolved yet. To explore the mechanism, we first subjected wild-type zebrafish to an exercise protocol validated for exercise-enhanced growth, and showed that exercised zebrafish, which indeed showed enhanced growth, had higher cortisol levels than the non-exercised controls. A central role was therefore hypothesized for the steroid hormone cortisol acting through the Glucocorticoid receptor (Gr). Second, we subjected wild-type zebrafish and zebrafish with a mutant Gr to exercise at optimal, suboptimal and super-optimal speeds and compared them with non-exercised controls. Exercised zebrafish showed growth enhancement at all speeds, with highest growth at optimal speeds. In the Gr mutant fish, exercise resulted in growth enhancement similar to wild-type zebrafish, indicating that cortisol cannot be considered as a main determinant of exercise-enhanced growth. Finally, the transcriptome of white skeletal muscle tissue was analysed by RNA sequencing. The results of this analysis showed that in the muscle tissue of Gr mutant fish a lower number of genes is regulated by exercise than in wild-type fish (183 versus 351). A cluster of 36 genes was regulated by exercise in both wild-type and mutant fish. In this cluster, genes involved in transcriptional regulation and protein ubiquitination were overrepresented. Since growth was enhanced similarly in both wild-type fish and mutants, these processes may play an important role in exercise-enhanced growth. Overall design: Deep-sequencing transcriptome analysis of white muscle samples derived from wild-type (++) or glucocorticoid receptor (Gr) mutant (--) Danio rerio specimens that were exposed to either a resting (REST) or a swimming (UOPT) regimen: wild-type resting (REST++; n=3), Gr mutant resting (REST--; n=3), wild-type swimming (UOPT++; n=3), Gr mutant swimming (UOPT--; n=3).
Publication Title
Cortisol Acting Through the Glucocorticoid Receptor Is Not Involved in Exercise-Enhanced Growth, But Does Affect the White Skeletal Muscle Transcriptome in Zebrafish (<i>Danio rerio</i>).
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples