Genetic factors contribute to the development of ischemic stroke but their identity remains largely unknown. We tested the association with ischemic stroke of 210 single nucleotide polymorphisms (SNPs) associated with pathways functionally related to stroke. We observed an association between the rs7956957 SNP in LRP1 and next performed microarrays analysis in healthy individuals to investigate possible associations of LRP genotypes with the expression of other genes.
Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.
Sex, Age, Specimen part
View SamplesSpontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH.
Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.
Sex, Age, Specimen part
View SamplesWe used microarrays to provide a transcriptomic signature of different types of cholestasis evoked by 3 different drugs and obstructive surgery
Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury.
Specimen part, Cell line, Treatment
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Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe analysed the RNA profile of IPSC-derived dopaminergic neurons from idiophatic and genetic form (LRRK2) of Parkinsons disease (PD). Both, idiopathic and genetic form of the disease show similar expression alterations and were merged in one whole PD group. We found 437 differentially expressed genes (DEGs) in the PD group as a whole. Up-regulated DEGs (n=254) encompassed genes involved in neural functions and transcription factor functions whereas down-regulated DEGs (n=183) affected basic homeostasis. These data point towards the presence of gene - and also protein - expression changes in DAn from PD patients which co-occur simultaneously along with DNA methylation changes.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage
View SamplesMicroglia constitutes a diverse population of cells that present a broad spectrum of responses when they become activated. Here, microglial status was studied under steady-state conditions from different brain regions involved in neurodegenerative diseases. Under basal conditions, midbrain microglia showed an immune-alert state not observed in striatum. Unique subpopulations of microglia expressing TLR4 and MHC-II with antigen presenting properties, and a higher proportion of infiltrating CD4+ T cells were identified in the midbrain. These results highlight that the inflammatory tone is context-dependent and reveal the unique properties of the midbrain related to the interaction with the immune system. Overall design: Analysis of two cohorts of control animals
Midbrain microglia mediate a specific immunosuppressive response under inflammatory conditions.
Age, Cell line, Subject
View SamplesGuillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy that debilitates the voluntary and autonomous response of the patient. In this study the transcriptome of peripheral blood mononuclear cells from a GBS patient and her healthy twin were compared to discover possible correlates of disease progression and recovery. Overall design: Blood samples were collected simultaneously from the Guillain-Barré patient (A) and from her control healthy twin (B) at three different time points during disease progression from hospitalization in the intensive care unit (T1), passing to intermediate care (T2), and at conclusion of locomotion rehabilitation program when the patient was close to abandon the hospital (T3).
Expression of Early Growth Response Gene-2 and Regulated Cytokines Correlates with Recovery from Guillain-Barré Syndrome.
No sample metadata fields
View SamplesThe combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of human iPSCs and could be used for therapeutic and regenerative medicine applications. In this study, we showed that a new first-in-class dual G9a/DNMT inhibitor CM272 compound improves the standard four-factor reprogramming efficiency of human fibroblast. The use of CM272 facilitates the generation of iPSC with only two factors, OCT4 and SOX2, allowing the removal of potentially oncogenic factors such as cMYC or KLF4. Taking a closer look at the early events occurring during cell reprogramming we demonstrated that treatment with our G9a/DNMT dual inhibitor induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to the genome and promotes mesenchymal to epithelial transition during cell reprogramming. Thus, the use of this new G9a/DNMT dual inhibitor compound may represent an interesting alternative for improving cell reprogramming.
Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.
Sex, Specimen part, Disease, Cell line
View SamplesS. epidermidis ability to form biofilms on indwelling medical devices and its association with the emergence of chronic infections is its main virulence factor. Nevertheless, it has been shown that the cells released from these biofilms are associated with the advent of serious acute infections with bacteraemia as one of the major clinical manifestations. Despite their clinical relevance, very little is known about the impact of biofilm-released cells in pathogenesis. Hence, herein, we characterized the murine immune response to the presence of cells released from S. epidermidis biofilms analysing spleen cells transcriptome by microarrays. These findings may help to explain the recurrent inflammatory symptoms presented by patients with colonization of indwelling medical devices.
<i>Staphylococcus epidermidis</i> Biofilm-Released Cells Induce a Prompt and More Marked <i>In vivo</i> Inflammatory-Type Response than Planktonic or Biofilm Cells.
Sex, Specimen part
View SamplesThe eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1) or promoting the resolution of RAD-51 double stranded DNA filaments (rfs-1 and helq-1) suggest that jmjd-5 prevents the formation of stalled postsynaptic recombination intermediates and favors RAD-51 removal. As these phenotypes are all recapitulated by a catalytically inactive jmjd-5 mutant, we propose a novel role for H3K36me2 regulation during late steps of homologous recombination critical to preserve genome integrity. Overall design: RNA sequencing of N2 and jmjd-5(tm3735) at 20C and 25C at generation 1 (G1) and generation 6 (G6)
JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
Subject
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