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.
Drosophila maleless gene counteracts X global aneuploid effects in males.
No sample metadata fields
View SamplesNeutrophils 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.
Transcriptional firing helps to drive NETosis.
Sex, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice.
Age, Specimen part
View SamplesChanges 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.
Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice.
Age, Specimen part
View SamplesWe 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.
CoA protects against the deleterious effects of caloric overload in Drosophila.
Sex, Specimen part, Subject
View SamplesAlthough 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.
Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN.
No sample metadata fields
View SamplesMucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. To identify transcriptional targets of the Hippo pathway in kidney we performed PTPN14 knockdown followed by RNA-seq in 2 kidney cancer cell lines (CAKI-1 and A-704) and a normal kidney epithelial cell line (HK-2). PTPN14 siRNAs were first functionally validated in a MCF-7 TEAD reporter luciferase stable cell line. Both siRNAs showed comparable knockdown efficiency and significantly increased luciferase reporter activity. In 2 of the kidney cell lines PTPN14 knockdown increased cell proliferation compared to non-target controls. While we observed excellent correlation between genes dysregulated by either PTPN14 or LATS1 knockdown within each cell line (HK2, CAKI-1 and A704), the overlap across the 3 cell lines was only 23 genes. Further, these 23 genes did not show concordant differential expression in MTSCC tumors. Overall, these results illustrate the marked tissue specificity of Hippo pathway targets.Finally, taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. Overall design: Cell lines (CAKI-1, HK2 or A704) were either transfected with 2 independent siRNAs or non-target controls. Forty eight hours post transcription total RNA was isolated and subjected to RNA-seq analysis
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesForced 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).
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>).
Specimen part, Treatment, Subject
View SamplesNew and effective therapeutical options are available for the treatment of Rheumatoid Arthritis. One of such treatments is rituximab, and chimeric anti-CD20 antibody that selectively depletes the CD20+ B cell subpopulation.
Identification of candidate genes for rituximab response in rheumatoid arthritis patients by microarray expression profiling in blood cells.
Specimen part, Disease, Disease stage
View SamplesStabilin-1/CLEVER-1 is a multidomain protein present in lymphatic and vascular endothelial cells and in M2 immunosuppressive macrophages. Stabilin-1 functions in scavenging, endocytosis and leukocyte adhesion to and transmigration through the endothelial cells. We have analyzed the putative functions of Stabilin-1 in blood monocytes and found that in healthy individuals 60-80% of both CD14+CD16- and CD14+C16+ monocytes, but not CD14dimCD16+ monocytes, expressed Stabilin-1 on the surface. Microarray and RNAseq analysis was performed to get more insight into the effect of Stabilin-1 expression on human monocytes transcriptome. Overall design: The transcriptome of human monocytes transfected with Stabilin-1 siRNA was compared to that of control siRNA transfected monocytes
Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes.
No sample metadata fields
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