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 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 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 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
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 7 colon tumor xenograft samples, 2 with diabetic mice and 5 with normal blood glucose levels. For xenograft model details see: Prieto I, et al. (2017) Colon cancer modulation by a diabetic environment: A single institutional experience. PLoS One 12(3):e0172300
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Specimen part
View SamplesBiotin is cofactor of crucial enzymes for intermediary metabolism, and its deficiency affects the transcription of some critical genes of mammalian glucose metabolism. However, the precise mechanisms of biotin starvation on gene expression are unknown. Here we show that metabolic changes ushered by deficiency of this vitamin sets in motion extensive reorganization of carbon metabolism gene expression, consistent across three diverse eukaryotes, that is mediated through a regulatory circuitry at the genome level similar in the three species.
Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).
Age, Specimen part
View SamplesGranulopoietic differentiation of myeloid progenitor cells derived from control iPSCs was performed in a two-step liquid culture. At the end of culture, stages of differentiation were identified by morphological analysis and submitted for RNA-sequencing analysis in order to provide insight into the genomic landscape of myeloid lineage hematopoiesis as modeled by the in vitro induced differentiation of iPSCs as compared to in vivo bone marrow-derived promyelocytes. Overall design: Peripheral blood from healthy controls was obtained and iPSC were generated from peripheral blood mononuclear cells. Hematopoietic progenitors generated from control iPSCs when cultured in myeloid expansion medium containing 50ng/mL SCF, 10ng/mL IL-3 and 10ng/mL GM-CSF for 5 days at which point cells were stained for CD45-Pacific blue, CD34-PECy7, CD33-AP, CD11b-APC-Cy7, CD15-FITC. 7-AAD was used to eliminate the dead cells. The promyelocytic population (CD45+CD34-CD33+CD11b-CD15+/lo) was sorted and the RNA from control iPSC promyelocytes was isolated using QIAGEN RNAeasy mini kit. The RNA samples were processed for RNA-seq analyses using RNA-seq protocol from NuGEN and Illumina. The amplified products were sequenced to analyze the gene expression profile of each replicate sample. A total of 20 samples were used in this analysis to characterize and compare iPSC in vitro differentiated myeloid cells with those isolated from human bone marrow.
p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Specimen part
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