Molecular mechanisms that influence susceptibility to multiple sclerosis are poorly understood. We conducted a gene expression study in healthy subjects that subsequently developed the disease. Gene expression profiles (HG U133A and A2, Affymetrix, 22,215 transcripts) of peripheral blood mononuclear cells were analyzed in 9 healthy subjects (mean age 19.8+1.1 years) up to 9 years (mean 5.11.2 years) before onset of MS (MS to be, MS2b), 11 age-, gender-, and origin-matched subjects that remained MS-free (MSf), and 31 clinically isolated syndrome (CIS) patients. Most informative genes (p<0.05) and significant biological processes were compared. 1051 genes (611 up-regulated, 440 down-regulated) were significantly different between MS2b and MSf subjects. MS2b signature was characterized by down-regulation of the nuclear receptor (NR) family genes including NR subfamily 4 group A member1 (NR4A1, p=0.01), member 3 (NR4A3, p=0.01), NR subfamily 2 group F member 2 (NR2F1, p=0.03) and vitamin D receptor (VDR, p=0.02), all known to be involved in T-cell regulation by apoptosis. Comparison between MS2b and CIS operating networks demonstrated evolution of the altered NR dependent apoptosis regulation. Decreased NR4A1 expression was verified at the mRNA and protein level in an independent cohort of 20 relapsing-remitting MS patients. The identified MS trait is associated with suppressed transcription of NR networks that leads to altered apoptosis of activated T cells and the development of clinical disease. MS2b subjects have already an ongoing process that eventually will lead to clinical disease and our finding are of importance as they suggest the possibility of early detection and prevention of MS.
Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of multiple sclerosis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic Potential in Early Gastric Cancer.
Age, Specimen part
View SamplesThe role of microbe in promoting the initiation of gastric cancer (GC), the third most lethal cancer worldwide, are ill-defined. Here, we found that tumor size and weight in gp130F/F mouse stomach at condition were significantly reduced compared to those of at SPF condition. To investigate the underlying mechanism and how host genes were regulated in the presence/absence of microbe, arrays were performed in stomach tissue from gp130F/F and WT at 4 week old at SPF and GF conditions.
Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic Potential in Early Gastric Cancer.
Age, Specimen part
View SamplesLeukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown.
Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells.
No sample metadata fields
View SamplesWhile the hypothalamo-pituitary-adrenal axis (HPA) activates a general stress response by increasing glucocorticoid (Gc) synthesis, biological stress resulting from infections triggers the inflammatory response through production of cytokines. The pituitary gland integrates some of these signals by responding to the pro-inflammatory cytokines IL6 and LIF and to a negative Gc feedback loop. The present work used whole-genome approaches to define the LIF/STAT3 regulatory network and to delineate cross-talk between this pathway and Gc action. Genome-wide ChIP-chip identified 3 449 STAT3 binding sites, whereas 2 396 genes regulated by LIF and/or Gc were found by expression profiling. Surprisingly, LIF on its own changed expression of only 85 genes but the joint action of LIF and Gc potentiated the expression of more than a thousand genes. Accordingly, activation of both LIF and Gc pathways also potentiated STAT3 and GR recruitment to many STAT3 targets. Our analyses revealed an unexpected gene cluster that requires both stimuli for delayed activation: 83% of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response.
Regulatory network analyses reveal genome-wide potentiation of LIF signaling by glucocorticoids and define an innate cell defense response.
Specimen part, Time
View SamplesWe used microarrays to detail the global programme of gene expression in embryonic stem cells, early differentiated embrioid bodies and effect of short-term ATRA treatment.
Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies.
Cell line
View SamplesDuring sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Drosophila maleless gene counteracts X global aneuploid effects in males.
No sample metadata fields
View SamplesThe focus of this study was to identify changes in host gene expression induced by the transcription-dependent function of the viral AC2 protein, and induced by the interaction of AC2/C2 with SnRK1.2 (AtAKIN11).
Altered expression of Arabidopsis genes in response to a multifunctional geminivirus pathogenicity protein.
Age, Specimen part, Treatment
View SamplesSpinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI.
Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training.
Time
View SamplesPitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Regulatory integration of Hox factor activity with T-box factors in limb development.
Specimen part, Cell line, Subject
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