This SuperSeries is composed of the SubSeries listed below.
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sex, Specimen part
View SamplesThese gene expression microarrays were performed as part of a project aiming to integrate quantitative proteomic, gene expression and epigenetic data from the childhood brain tumor medulloblastoma.
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sex, Specimen part
View SamplesA toxicogenomic analysis from liver of different pharmacological active coumarins (mammea A/BA+A/BB 3:1 and soulatrolide ) was performed on mice treated (20mg/kg/daily) for a whole week to evaluate if such compounds possess or could develop a hazardous profile on liver.
Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.
Sex, Specimen part, Treatment
View SamplesExon array profiling of human primary tumor tissue samples including breast, colon and NSCLC.
Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.
Specimen part
View SamplesA summary of the work associated to these microarrays is the following:
Gene expression profiles in rat mesenteric lymph nodes upon supplementation with conjugated linoleic acid during gestation and suckling.
Specimen part, Disease
View SamplesObesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein (HSD) or that has been supplemented with a rich source of saturated fat (HFD). These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline, such as decreased climbing ability. We subjected Oregon-R-C flies to variants of the HSD, HFD, or normal (control) diet (ND), followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. We targeted at least 50 million paired-end, stranded reads of 75 basepairs in size, and analyzed 4 biological replicates per dietary condition. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Functional annotation and enrichment analysis among genes whose expression was significantly affected by the obesogenic diets indicated an overrepresentation of genes associated with immunity, metabolism, and hemocyanin in the HFD group, and CHK, cell cycle activity, and DNA binding and transcription in the HSD group. Heat map representation of genes affected by both diets illustrated a large fraction of differentially expressed genes between the two diet groups. Diets high in sugar and diets high in fat both have notableeffects on the Drosophila transcriptome in head tissue. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation. Our results also indicate differences in the effects of the HFD and HSD on expression profiles in head tissue of Oregon-R-C flies, despite the reportedly similar phenotypic impacts of the diets. Overall design: Flies were reared on one of three diets (high fat, high sugar, or normal). 6 replicates, with twenty flies each, from each diet treatment were collected for a total of 18 samples. The heads of the flies were then obtained, and RNA extracted from each of those samples. 4 of the RNA samples from each diet group (12 samples total) were sequenced.
RNA-Sequencing of <i>Drosophila melanogaster</i> Head Tissue on High-Sugar and High-Fat Diets.
Specimen part, Subject
View SamplesWTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53 and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell cycle arrest, apoptosis, and p53-target gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.
The WTX tumor suppressor enhances p53 acetylation by CBP/p300.
Cell line
View SamplesThe small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) vs. distal (cauda) epididymis, then characterized development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, and subsequently implant inefficiently and fail soon after implantation. Remarkably, microinjection of purified cauda-specific small RNAs into caput-derived embryos not only completely rescued preimplantation molecular defects, but also suppressed the postimplantation embryonic lethality phenotype. These findings reveal an essential role for small RNA remodeling during post-testicular maturation of mammalian sperm, and identify a specific preimplantation gene expression program responsive to sperm-delivered microRNAs. Overall design: Zygotes were generated by ICSI from sperm isolated from the testis, caput epididymis, or cauda epididiymis. Following fertilization by ICSI zygotes were developed to different stages of preimplantation development and were harvested for single-embryo RNA-Seq (Smart-Seq 2 protocol). For RNA injection experiments 3 hours after fertilization by ICSI RNA was injected using an Eppendorf Femtojet injection setup.
Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice.
Cell line, Subject
View SamplesThe study was designed in order to identify genes differentially expressed when glucocorticoid signaling is blocked by a glucocorticoid-receptor antagonist (RU486 mifepristone) in the context of brain inflammation induced by bacterial lipopolysaccharide (LPS). LPS is only able to cause murine brain damage in our experimental conditions upon RU486 pre-treatment. Hence, the study may reveal potential candidate genes to mediate neuroprotection or neurotoxicity. Due to the factorial design of the experiment, RU486 main-effect could be dissociated from the effects resultant of RU486/inflammation interaction. In addition, brain dissection was conducted to verify the effects in the brain side ipsilateral or contralateral to the site of intracerebral LPS infusion.
Genes involved in the balance between neuronal survival and death during inflammation.
Sex, Age, Specimen part
View SamplesThe bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPa, C/EBPß, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. Moreover, chemical inhibition of BET bromodomains is found to suppress the functional output each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and Brd4, which supports leukemia maintenance and is suppressed by BET bromodomain inhibition. Overall design: PolyA selected RNA-Seq for drug treated or shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)
BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia.
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