This SuperSeries is composed of the SubSeries listed below.
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Age
View SamplesThe contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 8.9). Tumors were classified as low (mean = 0.5 0.6, n = 11), medium (mean = 5.4 2.4, n = 10), or high (mean = 19.2 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Age
View SamplesAlthough Human papillomavirus infection is the main causal factor for cervical cancer (CC), there is data suggesting genetic factors could modulate the risk and progression of CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to cervical cancer, HPV infection and HPV types, a case-control study was performed in the Mexican mestizo population. The polymorphism of mtDNA D-Loop was investigated in 187 cervical cancer patients and 270 healthy controls. D-loop was amplified from a blood DNA sample and analyzed by sequencing. HPV was detected and typed in cervical scrapes from both groups. mtDNA polymorphisms were compared in the whole samples and stratified by HPV types. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (OR=1.6, 95% CI: 1.05-2.58) and showed an additive effect of 36% over the risk conferred by the HPV (OR=153, 95% CI: 65.4-357.5). The frequency of HPV 16, 18, 31 and 45 in cancer samples was similar in all haplogroups but one (D1). It showed a very low frequency of HPV16, any HPV18 and high frequency of HPVs 31, 45 and other types. Two mtDNA genes (MT-TD, MTTK) could be involved in the increased risk conferred by the haplogroup B2, since they were up-regulated exclusively in B2 tumors (p<0.05, t-test). These findings will contribute to clarify the importance of genetic factors in CC.
The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
Specimen part
View SamplesTargets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Treatment
View SamplesPurpose: using RNA-seq as a screening tool to determine candidate genes of interest within a genetically defined neural subpopulation in the zebrafish embryonic spinal cord. Results: The early embryonic spinal cord displays patterns of spontaneous activity that generate the earliest motor behavior in the zebrafish. We show the behavior and the neural activity to be inhibited by environmental levels of light. Since at these young ages the fish is blind, and since restricted illumination patterns on the trunk of the fish can elicit a photo-response, we hypothesized that the photo-inhibition is an intrinsic property of the active central pattern generator network within the spinal cord. We FACS-isolated cells from this network as well as those from a panneuronal population and sequenced mRNAs. Through differential expression analysis we identified vertebrate ancient long opsin a as a candidate and then further validated its function in the circuit through knockdown and rescue experiments. Overall design: RNA sequencing of 2 FACS purified neural populations from zebrafish spinal cord.
A spinal opsin controls early neural activity and drives a behavioral light response.
No sample metadata fields
View SamplesThe adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging.
Lnk deficiency partially mitigates hematopoietic stem cell aging.
Specimen part
View SamplesTHREE INDEPENDENT REPLICATES AND ARE THE CONTROL NON-INFECTED CELLS:
Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum.
No sample metadata fields
View SamplesRecessive retinitis pigmentosa (RP) is often caused by nonsense mutations that lead to low mRNA levels as a result of nonsense-mediated decay. Some RP genes are expressed at detectable levels in leukocytes as well as in the retina. We designed a microarray-based method to find recessive RP genes based on low lymphoblast mRNA expression levels
Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.
No sample metadata fields
View SamplesA key requisite for the success of a dendritic cell (DC)-based vaccine in treating malignancies is the capacity of the DCs to attract immune effector cells for further interaction and activation, considering crosstalk with DCs is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC therapy. In this paper we examine if the so-called interleukin (IL)-15 DC vaccine provides a favorable chemokine milieu for recruiting T cells, natural killer (NK) cells and gamma delta () T cells, in comparison with the IL-4 DCs used routinely for clinical studies, as well as the underlying mechanisms of immune cell attraction by IL-15 DCs. Chemokine signaling is studied both at the RNA level, using microarray data of mature DCs, and functional level, by means of a transwell chemotaxis assay. Important to note, the classic IL-4 DC vaccine falls short to attract the required immune effector lymphocytes, whereas the IL-15 DCs provide a favorable chemokine milieu for recruiting all cytolytic effector cells. The elevated secretion of the chemokine (C-C motif) ligand 4 (CCL4), also known as macrophage inflammatory protein-1 (MIP-1), by IL-15 DCs underlies the enhanced migratory responsiveness of T cells, NK cells and T cells. Namely, neutralizing its receptor CCR5 resulted in a significant drop in migration of the aforementioned effector cells towards IL-15 DCs. These findings should be kept in mind in the design of future DC-based cancer vaccines.
Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.
Specimen part, Subject
View SamplesThe transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the ß-blocker atenolol (ATE) and the ß-agonist isoproterenol (ISO). Differential expression analyses revealed a large set of genes responding to ISO (n=1770 at FDR=0.0001) and a comparatively small one responding to ATE (n=23 at FDR=0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r= -0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibited coherent transcription profiles across some strains and/or treatments. Correlations between such modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Our study provides new insights into the transcriptional response of the heart to perturbations of the ß-adrenergic system, implicating several new genes that had not been associated to this system previously. Overall design: Cardiac mRNA expression profiles of the various inbred mouse strains were examined either under baseline condition (control) or in response to chronic administration of isoproterenol or atenolol at 10 mg/kg per day for 2 weeks. Expression data were produced by RNA-sequencing, in triplicates, using the HiSeq 2000 Illumina platform. Only males, aged ten to twelve weeks on average, were included in the experimental protocol. Mouse ID numbers refer to those described in Berthonneche C. et al. PLoS One. 2009 Aug 12;4(8):e6610 (doi: 10.1371/journal.pone.0006610. PMID: 19672458). Corresponding individual phenotypic values, in particular heart rate, systolic blood pressure, electrocardiogaphic measurements and heart weight are available in dataset "maurer1" of the Mouse Phenome Database (http://phenome.jax.org/). Preparation of the sequencing libraries, RNA-sequencing and RNA expression quantitations were performed by the BGI.
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Sex, Specimen part, Treatment, Subject
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