Affimetrix Human Gene 1.1 ST Array profiling of 763 primary medullobalstoma samples used for identification of Medullobastoma subtypes
Intertumoral Heterogeneity within Medulloblastoma Subgroups.
Specimen part
View SamplesThe mechanisms of action of the combined targeted therapy bevacizumab erlotinib in late stage non-squamous non-small cell lung cancer was investigated by means of whole genome exon arrays.
24h-gene variation effect of combined bevacizumab/erlotinib in advanced non-squamous non-small cell lung cancer using exon array blood profiling.
Sex, Age, Specimen part, Time
View SamplesPeripheral whole blood-based gene expression profiling has become one of the most common strategies exploited in the development of clinically relevant biomarkers. However, the ability to identify biologically meaningful conclusions from gene expression patterns in whole blood is highly problematic. First, it is difficult to know whether or not expression patterns in whole blood capture those in primary tissues. Second, if explicit steps are not taken to accommodate the extremely elevated expression levels of globin in blood then large-scale multi-probe microarray-based studies can be severely compromised. Many studies consider the use of mouse blood as a model for human blood in addition to considering blood gene expression levels as a general surrogate for gene expression levels in other tissues. We explored the effects of globin reduction on peripheral mouse blood in the detection of genes known to be expressed in human tissues. Globin reduction resulted in 1.) a significant increase in the number of probes detected (5840 944 vs 12411 1904); 2.) increased expression for 4128 probe sets compared to non-globin reduced blood (p < .001, two-fold); 3.) improved detection of genes associated with many biological pathways and diseases; and 4.) an increased ability to detect genes expressed in 27 human tissues (p < 10-4). This study suggests that although microarray-based mouse blood gene expression studies that do not consider the effects of globin are severely compromised, globin-reduced mouse whole blood gene expression studies can be used to capture the expression profiles of genes known to contribute to various human diseases.
The effects of globin on microarray-based gene expression analysis of mouse blood.
Sex, Age, Specimen part
View SamplesWe characterized the Drosophila third instar eye disc using single cell RNA-seq and labelled the multiple cell populations. The results identified a novel transcriptional switch in photoreceptors relating to axonal projections. We then performed single cell RNA-seq on rbf (Rb) mutants and compared the results to the WT cell populations. This identified a specific cell population only in the Rb mutant tissue. This cell population has an upregulation of HIF1A and glycolitic genes such as Aldolase and Lactate dehydrogenase. As a result these cells produce lactate and undergo apoptosis. We also show this process to be directly regulated by E2F/Dp. The paper uncovers a novel metabolic aspect of Rb/E2F dependent apoptosis. Overall design: examining WT and Rb mutants third instar eye disc using single cell RNA-seq
Single cell RNA-sequencing identifies a metabolic aspect of apoptosis in Rbf mutant.
Specimen part, Subject
View SamplesChronic biomechanical stress elicits remodeling of the arterial wall and causes detrimental arterial stenosis and stiffening. In this context, molecular determinants controlling proliferation and stress responses of vascular smooth muscle cells (VSMCs) have been insufficiently studied. We identified the transcription factor nuclear factor of activated T-cells 5 (NFAT5) as crucial regulatory element of mechanical stress responses of VSMCs. The relevance of this observation for biomechanically induced arterial remodeling was investigated in mice upon SMC-specific knockdown of NFAT5. While blood pressure levels, vascular architecture and flow-induced collateral growth were not affected in these mice, both hypertension-mediated arterial thickening and muscularization of pulmonary arteries during pulmonary artery hypertension (PAH) were impaired. In all models, a decrease in VSMC proliferation was observed indicating that NFAT5 controls activation of VSMCs in the remodeling arterial wall. Mechanistically, mechanoactivation of VSMCs promotes nuclear translocation NFTA5c upon its phosphorylation at Y143 and dephosphorylation at S1197. As evidenced by transcriptome studies, loss of NFAT5 in mechanoactivated VSMCs impairs expression of gene products controlling cell cycle and transcription/translation. These findings identify NFAT5 as molecular determinant of VSMC responses to biomechanical stress and arterial thickening.
NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle Cells.
Treatment
View SamplesWhite Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broilers fillets present an impaired visual appearance that negatively affects consumers acceptability. Previous studies have highlighted in affected fillets a deeply damaged muscle, showing profound inflammation, fibrosis and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 Pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further define the transcription patterns associated to these myopathies.
Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.
Sex, Specimen part
View SamplesWhy we sleep is still one of the most perplexing mysteries in biology. Strong evidence, however, indicates that sleep is necessary for normal brain function and that the need to sleep is a tightly regulated process. Surprisingly molecular mechanisms that determine the need to sleep are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need.
Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex.
Sex, Age, Specimen part
View SamplesRibosome assembly in eukaryotes involves the activity of hundreds of assembly factors that direct the hierarchical assembly of ribosomal proteins and numerous ribosomal RNA folding steps. However, detailed insights into the function of assembly factors and ribosomal RNA folding events are lacking. To address this, we have developed ChemModSeq, a method that combines structure probing, high throughput sequencing and statistical modeling, to quantitatively measure RNA structural rearrangements during the assembly of macromolecular complexes. By applying ChemModSeq to purified 40S assembly intermediates we obtained nucleotide-resolution maps of ribosomal RNA flexibility revealing structurally distinct assembly intermediates and mechanistic insights into assembly dynamics not readily observed in cryo-electron microscopy reconstructions. We show that RNA restructuring events coincide with the release of assembly factors and predict that completion of the head domain is required before the Rio1 kinase enters the assembly pathway. Collectively, our results suggest that 40S assembly factors regulate the timely incorporation of ribosomal proteins by delaying specific folding steps in the 3’ major domain of the 20S pre-ribosomal RNA. Overall design: Three datasets of yeast ribosomal samples subjected to different chemical modifications; 1M7 dataset contains 8 different modified samples and 2 control samples; NAI dataset contains 3 different modified samples and 2 control samples; DMS dataset contains 1 modified sample and 1 control sample. Each sample consists of at least two replicates.
Snapshots of pre-rRNA structural flexibility reveal eukaryotic 40S assembly dynamics at nucleotide resolution.
Disease, Cell line, Treatment, Subject
View SamplesA novel mouse line was found to exhibit prominent mechanosensory deficits both behaviorally and at the primary sensory afferents, and exhibits decreased ATP release from the skin.
Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes.
Specimen part
View SamplesThe origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences.
Elevated gene expression levels distinguish human from non-human primate brains.
Sex, Age, Specimen part
View Samples