Background: In multiple sclerosis (MS), immune up-regulation is coupled to subnormal immune response to interferon-β (IFN-β) and low serum IFN-β levels. The relationship between the defect in IFN signalling and acute and long-term effects of IFN-β on gene expression in MS is inadequately understood. Methods: We profiled IFN-β-induced transcriptome shifts, using high-resolution microarrays on 227 mononuclear cell samples from IFN-β-treated MS Complete Responders (CR) stable for five years, and stable and active Partial Responders (PR), stable and active untreated MS, and healthy controls. Findings: IFN-β injection induced short-term changes in 1,200 genes compared to baseline expression after 4-day IFN washout. Pre-injection after washout, and in response to IFN-β injections, PR more frequently had abnormal gene expression than CR. Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes (ILT, IDO1, PD-L1). Expression of 8,800 genes was dysregulated n therapy-naïve compared to IFN-β-treated patients. These long-term changes in protein-coding and long non-coding RNAs affect immunity, synaptic transmission, and CNS cell survival, and correct the disordered therapy-naïve transcriptome to near-normal. In keeping with its impact on clinical course and brain repair in MS, long-term IFN-β treatment reversed the overexpression of proinflammatory and MMP genes, while enhancing genes involved in the oligodendroglia-protective integrated stress response, neuroprotection, and immunoregulation. In the rectified long-term signature, 277 transcripts differed between stable PR and CR patients.
Interferon-β corrects massive gene dysregulation in multiple sclerosis: Short-term and long-term effects on immune regulation and neuroprotection.
Age, Specimen part
View SamplesThe seed coat of black (iRT) soybean with the dominant R allele begins to accumulate cyanic pigments at the transition stage of seed development (300 400 mg fresh seed weight), whereas the brown (irT) nearly-isogenic seed coat with the recessive r allele lacks cyanic pigments at all stages of seed development.
Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max) seed coats enabling the identification of pigment isogenes.
Specimen part
View SamplesEstrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells. Overall design: RNA-seq was used to study the effects of the D538G mutation on gene expression
Estrogen-independent molecular actions of mutant estrogen receptor 1 in endometrial cancer.
Cell line, Treatment, Subject, Time
View SamplesMesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1M) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1M and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells.
Specimen part
View SamplesWe report the transcriptome changes that result of the genomic deletion of one or two alleles of an islet-specific long non-coding RNA (Blinc1) in isolated pancreas from e15.5 mouse embryos. Overall design: Pancreas from e15.5 embryos were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq.
βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Specimen part, Subject
View SamplesThe acute response four hours after a fat load of extra virgin olive oil was investigated using DNA microarrays. Hepatic gene expression was analysed in Wistar Rats.
Postprandial transcriptome associated with virgin olive oil intake in rat liver.
Sex, Age, Specimen part
View SamplesThe hypothesis that the oleanolic acid of olive oil might influence hepatic gene expression in an apoE was tested in mice.
Dietary oleanolic acid mediates circadian clock gene expression in liver independently of diet and animal model but requires apolipoprotein A1.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesTo investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesBoth diploid RPE-1 and BJ-1 cells were made tetraploid by transient treatment with the cytokinesis inhibitor DCD. Proliferating tetraploids from both BJ-1 and RPE-1 were selected and isolated. The gene expression profiles of the proliferating tetraploid cells were then compared to the diploids from which they originated.
Cytokinesis failure triggers hippo tumor suppressor pathway activation.
Specimen part
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