We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.
Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesAffymetrix gene expression analysis was carried out to investigate the differences in gene profile of MBP89-101-reactive encephalitogenic T cells before and after co-culture with cerebellar granular neurons (CGNs). Co-culture of MBP89-101-reactive encephalitogenic T cells with CGNs leads to generation of T cells with regulatory T cells phenotype (CD4+CD25+membrane bound TGF-b+ T cells) or a new regulatory phenotype (CD4highPD-L1high T cells). CGN-induced CD4+CD25+membrane bound TGF-b+ T regulatory cells, CD4highPD-L1high T cells were purified by FACSAria. IFN-beta induced T lymphocytes (CD4highPD-L1high T cells) were also FACSAria purified. All these populations were compared to MBP89-101-reactive encephalitogenic T cells. Samples were prepared from biological triplicates for each FACSAria sorted population.
FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS.
Specimen part
View SamplesA genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes.
Gender-associated differences of perforin polymorphisms in the susceptibility to multiple sclerosis.
Sex, Specimen part, Disease
View SamplesWe compared the transcriptomes of isogenic diploid fibroblasts expressing progerin or elevated levels of wild-type prelamin A with that of wild-type fibroblasts. We subsequently used the reversion towards normal of two phenotypes, reduced cell growth and dismorphic nuclei, by treatment with farnesyltransferase inhibitor (FTI) or overexpression of ZMPSTE24, as a filtering strategy to identify genes linked to the onset of these two phenotypes.
A filtering strategy identifies FOXQ1 as a potential effector of lamin A dysfunction.
Specimen part, Cell line, Treatment
View SamplesIt has been shown previously that endothelial cells and LepR+ stromal cells are the main sources of SCF in vivo in the mouse bone marrow. We tested whether SCF from endothelial cells and/or LepR+ stromal cells is important for the maintenance of hematopoietic progenitors and erythroid progenitors in mouse bone marrow by conditional deletion of Scf from these two cell types. We discovered that Scf deletion from LepR+ stromal cells, but not endothelial cells, reduced the numbers of hematopoietic progenitors and erythroid progenitors in mice. We performed RNA-Seq on PreCFU-E and CFU-E progenitors from control mice and from mice with Scf deletion from LepR+ stromal cells. We discovered that lack of SCF from LepR+ cells induces a premature differentiation of PreCFU-E and CFU-E progenitors. Overall design: Examination of gene expression profile in 2 cell tyeps from 3 different genetic backgrounds
Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow.
Sex, Specimen part, Subject
View SamplesSingle O-GlcNAc modification orchestrate by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA alias MGEA5) enzymes, affects signal transduction and gene expression by chromatin modulation. We developed Oga deleted MEF (mouse embryonic fibroblast) cells to investigate effects of O-GlcNAc modification in mice. RNA isolated from Mouse Embryonic Fibroblast cells generated from Oga Knock out (KO) Heterozygous (Het) and wild type (WT) cells and subjected to microarray analysis.
Conditional knock-out reveals a requirement for O-linked N-Acetylglucosaminase (O-GlcNAcase) in metabolic homeostasis.
Sex, Specimen part
View SamplesProstate cancer is dependent on androgen receptor (AR) signaling at all stages of the disease and cyclin D1 has been shown to negatively modulate the expression of the AR-dependent gene prostate specific antigen (KLK3/PSA).
Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function.
Cell line, Treatment
View SamplesWe are investigating the transcriptional response of changes in RNA steady-state levels between normal and DM1.
RNA steady-state defects in myotonic dystrophy are linked to nuclear exclusion of SHARP.
Specimen part
View SamplesBAF57, a component of the SWI/SNF chromatin remodeling complex conglomerate,modulates androgen receptor activity to promote prostate cancer. However the molecular consequences of tumor associated BAF57 elevation have remianed undefined in advanced disease such as castration resistant prostate cancer and/or metastasis
Aberrant BAF57 signaling facilitates prometastatic phenotypes.
Specimen part, Treatment
View SamplesWe isolated RNA from sorted common myeloid progenitor cells from wild-type fetal liver, wild-type adult bone marrow, transgenic Lin28b bone marrow, let-7b/c knock-out bone marrow, and Lin28b-deficient fetal liver and compared mRNA expression profiles. Overall design: Examination of mRNA expression in common myeloid progenitors from multiple developmental time points and genotypes. Please note that iLin28* samples represent Lin28-induced samples, while the iLin28_*_vavcre samples represent hematopoietic-specific induction of Lin28.
Developmental regulation of myeloerythroid progenitor function by the Lin28b-let-7-Hmga2 axis.
Specimen part, Cell line, Subject
View Samples