We 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
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
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 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Sex, Specimen part, Cell line
View SamplesHistone deacetylases (HDACs) have been identified as therapeutic targets due to regulatory function in DNA structure and organization. We have analyzed the role of the LBH589, a novel pan inhibitor of class I and II HDACs, in Acute Lymphoblastic Leukemia. In vitro, LBH589 was shown to induce a dose dependent antiproliferative and apoptotic effect which was associated with an increase in the acetylation of H3 and H4 histone acetylation which was uniformly in every genetic subgroup of ALL. In vivo administration of LBH589 in BALB/c-RAG2-/-c-/- mice in which T and B-cell leukemic cell lines were injected induced a significant reduction in tumor growth (TOM-1, p<0.01 and MOLT-4 p<0.05). Leukemic cells from patients were employed to establish a xenograft model of human leukemia in BALB/c-RAG2-/-c-/- mice and further transplanted in consecutive generations of mice. Treatment of these xenografts with LBH589 induced an increase in the acetylation of H3 and H4 and prolonged the survival of mice in comparison with the animals treated with Vincristine and Dexametasone (p<0.05) and this effect was significantly higher when LBH589 was combined with Vincristine and Dexametasone (p<0.001). Our results that the use of LBH589 in combination with standard chemotherapy represents an attractive option for treatment of patients with ALL.
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Cell line
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 SamplesIdentify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE).
Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy.
Specimen part, Treatment
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