The resistance of CML leukemic stem cells (LSC) to tyrosine kinase inhibitor therapies targeting BCR-ABL leads to persistence of disease in most cases. We have identified novel putative therapeutic targets that are differentially expressed in CML LSCs compared to normal hematopoietic stem cells (HSC) by transciptional profiling of stem and progenitor cell populations from CML patients and normal donors.
Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations.
Specimen part, Disease, Disease stage
View SamplesThe primary goal of this study was to assess differences in gene expression between prostate cancer cell lines and normal prostate epithelial and stromal cells in primary culture.
DNA hypomethylation arises later in prostate cancer progression than CpG island hypermethylation and contributes to metastatic tumor heterogeneity.
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View SamplesOptic neuritis (ON) is a common manifestation of multiple sclerosis (MS); it appears as the presenting symptom in about 25% of MS patients and occurs in 3070% of patients with MS during the course of their illness
The role of B cells in the early onset of the first demyelinating event of acute optic neuritis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesSpontaneous neural repair from endogenous neural stem cells (NSCs) occurs in response to central nervous system (CNS) injuries or diseases to only a limited extent from endogenous NSCs niches. Uncovering the mechanisms that control neural repair and can be further manipulated to promote towards oligodendrocyte progenitors cells (OPCs) and myelinating oligodendrocytes is a major objective.
Prickle1 as positive regulator of oligodendrocyte differentiation.
Sex, Age, Specimen part, Time
View SamplesMicroarray experiments were carried out to ascertain whether TOP2 is required for DHT induced androgen receptor target gene expression. We investigated the effect of pharmacological inhibition or RNA interference-mediated depletion of TOP2 on gene expression in androgen-dependent LNCaP prostate cancer cells.
Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements.
Cell line
View SamplesBackground: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable treating physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods: In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results: We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p< 0.001). If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used, resulting in a prediction with a resolution of 50 days as to the timing of the next relapse. The error rate of this predictor was 2.3 fold lower than the error rate of random predictions (error rate = 0.35, p<0.001). The predictors were further evaluated and found effective not only in untreated patients but were also valid for MS patients which subsequently received immunomodulatory treatments after the initial testing (the error rate of the first level predictor was < 0.18 with p<0.001 for all the patient groups). Conclusions: We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature
Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesMolecular 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 SamplesBackgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Subject
View SamplesInterferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available.
Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis.
Sex, Age, Treatment
View SamplesRNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells. Overall design: Splenic follicular IgD low and IgD high , and MZ B cells were sorted by FACS from naïve 8-10 weeks old mice. Total RNA was isolated from the sorted cells using RNAqueous® -4PCR kit and RNA sequencing was performed. Splenocytes from five mice were pooled for each sorting. Three independent sorting was performed for each B cell subset.
Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.
Specimen part, Cell line, Subject
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