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 SamplesAtrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts.
Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.
Specimen part
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 SamplesWe elucidate a neurological syndrome affecting both the PNS and CNS defined by CLP1 mutations that impair tRNA splicing Overall design: Identification and biochemical characterization of mutant CLP1 in human patients
Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.
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 SamplesThis is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of them with T2DM. Using gene set enrichment, we identified an unexpected overlap of pathways over-represented in diabetics compared to non-diabetics, both in tumor and normal mucosa, including diabetes-related metabolic and signaling processes. An integration with other -omic studies suggests that in diabetics, the local micro-environment in normal colon mucosa may be a factor driving field cancerization which may promote carcinogenesis. Several of these pathways converged on the tumor initiation axis TEAD/YAP-TAZ. Cell culture studies confirmed that high glucose concentrations upregulate this pathway in non-tumor colon cells. In conclusion, diabetes is associated to deregulation of cancer-related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support the existence of the field of cancerization paradigm in diabetes and set a new framework to study link between diabetes and cancer.
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Specimen part
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