Background: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM.
Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas.
Specimen part, Disease
View SamplesTo explore the primary cause of Dilated Cardiomyopathy in heart samples from DCM-diagnosed patients who had undergone heart transplant (hDCM), we set out to identify differentially expressed genes by massively parallel sequencing of heart samples. Overall design: Methods: Heart mRNA profiles from DCM-diagnosed patients who had undergone heart transplant (hDCM) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.
No sample metadata fields
View SamplesTo explore the primary cause of Dilated Cardiomyopathy in Bmi1-null mice, we set out to identify differentially expressed genes by massively parallel sequencing of heart samples from Bmi1f/f;aMHCTM-Cretg/+ mice versus aMHCTM-Cretg/+ control mice (17 weeks postinduction). Overall design: Methods: Heart mRNA profiles of 17-weeks post-induction Bmi1f/f; MHCTM-Cretg/+ mice and MHCTM-Cretg/+ control mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. Sequence reads were pre-processed with Cutadapt 1.2.1, to remove TruSeq adapters and mapped on the mouse transcriptome (Ensembl gene-build GRCm38.v70) using RSEM v1.2.3. The Bioconductor package EdgeR was used to normalize data with TMM and to test for differential expression of genes using GLM.
Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.
No sample metadata fields
View SamplesHIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable. Overall design: RNA-seq was performed to identify up- or down-regulated genes associated with in vitro resistance to R5-tropic viruses in activated CD4+ T cells from HIV+ Elite Controllers and family members
Transcriptional down-regulation of <i>ccr5</i> in a subset of HIV+ controllers and their family members.
Specimen part, Subject
View SamplesElevated fructose consumption has been associated with metabolic and renal diseases. It is controversial whether kidney problems are a result of systemic metabolic disease or stem, at least in part, from changes due to local fructose metabolism. To study the short-term effect of fructose on genetic programs in renal proximal tubules, the diet for rats in experimental groups was supplemented for 7 days with 20% fructose in the drinking water. Two sets of 8 rats each on different baseline rodent diets were used in this study. 4 animals of each set received fructose in the drinking water while the other 4 served as controls. Animals were sacrificed after the experimental period of 7 days and slices of superficial kidney cortex were used for total RNA extraction. The RNA was analyzed with Affymetrix RaGene-2_0-st.
Transcriptome signature for dietary fructose-specific changes in rat renal cortex: A quantitative approach to physiological relevance.
Sex, Age, Specimen part
View SamplesNoval and traditional signaling pathways involved in cervical ripening that were regulated by MPA were identified.
Preventing cervical ripening: the primary mechanism by which progestational agents prevent preterm birth?
No sample metadata fields
View SamplesThis study takes on the problem of bridging transcriptional data to neuronal phenotype and function by using publicly available datasets characterizing distinct neuronal populations based on gene expression, electrophysiology and morphology. In addition, a non-published PatchSeq dataset of Pvalb-cre positive cells in CA1 was used, which is the dataset submitted here. Taken together, these datasets were used to identify cross-cell type correlations between these data modalities. Detected correlations were classified as “class-driven” if they could be explained by differences between excitatory and inhibitory cell classes, or “non-class driven” if they could be explained by gradient like phenotypic differences within cell classes. Some genes whose relationships to electrophysiological or morphological properties were found to to be specific to either excitatory or inhibitory cell types. The Patch Seq data specifically allowed simultaneous single-cell characterization of gene expression and electrophysiology, showing that the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. Overall design: Patchseq data was collected from single cells of the mouse hippocampus CA1 in order to investigate correlations between gene expression patterns and electrophysiological properties of various interneuron cell classes 19 individual cells Re-analysis details included in supplementary file readme.txt.
Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes.
Age, Specimen part, Subject
View SamplesA loss of StarPap would be predicted to result in a decrease in cellular levels of mRNAs which it polyadenylates. Moreover, if PIPKIalpha has a function relationship with StarPap, knockdown of PIPKIalpha should cause a decrease in a pool of target mRNAs which require both StarPap and PIPKIalpha for their maturation. To test this, we independently knocked down StarPap and PIPKIalpha, and performed microarray analysis of total polyadenylated mRNAs from each group.
A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs.
No sample metadata fields
View SamplesMethods of reprogramming somatic cells to an induced pluripotent state (iPSC) have enabled the direct modeling of human disease and ultimately promise to revolutionize regenerative medicine. iPSCs offer an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests and importantly for regenerative medicine, and already have been employed to unmask novel insights into human diseases. While iPSCs can be consistently generated through overexpression of the four Yamanaka Factors OCT4, SOX2, KLF4 and c-MYC (OSKM), reprogrammed cells present worrisome differences with embryonic stem cells in transcriptional and epigenetic profiles, as well as developmental potential and difficulties in cell culturing. A thorough mechanistic understanding of the reprogramming process is critical to overcoming these barriers to the clinical use of iPSC. We have recently published a novel factor combination based on molecules specifically enriched in the metaphase II human oocyte. We have shown that just the overexpression of histone-remodeling chaperone ASF1A and OCT4 in hADFs previously exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells (AO9-iPSCs). Our study contributes to the understanding of the molecular pathways governing somatic cell reprogramming. Here we want to go deeper in the reprogramming mechanisms by understanding the importance of somatic cell origin, and analyzing (and establishing comparison with) the transcriptional and epigenetic characteristics of AO9-iPSCs. As the intrinsic histone chaperone activity of ASF1A and our data indicate, these cells could be closer to the embryonic pluripotent state, with less epigenetic memory, better culture properties and differentiation potential.
Analysis of Menstrual Blood Stromal Cells Reveals SOX15 Triggers Oocyte-Based Human Cell Reprogramming.
Sex, Specimen part, Subject
View SamplesTo investigate the role of miR-29b on the changes in expression of genes involved in the synthesis and deposition of extracellular matrix in human trabecular meshwork cells (HTM).
Role of miR-29b on the regulation of the extracellular matrix in human trabecular meshwork cells under chronic oxidative stress.
Cell line
View Samples