Our results introduce interleukin (IL)-11 as a new cytokine that may play a role in the development of the autoimmune response in patients with relapsing remitting multiple sclerosis (RR MS). IL-11 was found to be the highest up-regulated cytokine in the serum and cerebrospinal fluid (CSF) from patients with clinically isolated syndrome (CIS) suggestive of MS. It was also increased in the serum and CSF of patients with clinically definitive RRMS and during the clinical relapses of the disease. CD4+ cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11+CD4+ cells is significantly increased in CIS patients in comparison to healthy controls (HCs). Furthermore, we have identified IL-11 as a new Th17-promoting cytokine. IL-11 induces a differentiation of nave CD4+ T cells into Th17 cells, as well as Th17 memory cell expansion, characterized by secretion of IL-17A, IL-17F, IL-21 and IL-22. Since the Th17 cytokines IL-17F, IL-21 and TNF- induced differentiation of nave cells in the IL-11-secreting CD4+ cells, we propose that cross-talk between IL-11+CD4+ and Th17-cells may play a role in the initiation and propagation of the autoimmune response in RRMS.
IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.
Specimen part
View SamplesThe mitochondrial respiratory chain is composed of lipoprotein complexes imbedded in the inner mitochondrial membrane. This chain of enzymes transfers electrons from NADH and FADH2, provided from divers metabolic pathways, to oxygen. It couples the transfer of electrons to the translocation of protons across the membrane. Several clinical syndromes have been associated with respiratory dysfunction caused by mitochondrial or nuclear mutations. A number of mutations in the mitochondrial genes encoding for cytochrome b (CYTB) and cytochrome oxidase (COX 1, 2 and 3) have been linked with diseases. We are using yeast mutants to characterize the deleterious effect of mutations reported in patients on the assembly and catalytic properties of the affected enzymes, and to study the impact of mutations in nuclear genes, such as OXA1, encoding for factors required for the assembly of the respiratory complexes. In this work, we monitored the effects of the mutations causing respiratory defect on the whole genome expression. We compared the change in gene expression in rho0 cells (with a complete deletion of the mitochondrial genome, and by consequence without respiratory chain), in cells with either a single defective enzyme or several, and in cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin. The impact of the mutations on the respiratory function ranged from mild to severe. The expression of approx. 350 genes was changed in at least one mutant. Cluster analysis was performed using the Cluster program (Eisen, 1998, PNAS 95:14863). Four groups of genes were studied in more details: Group A, the most repressed genes; Group B, the most over-expressed genes; Group C, genes more repressed in rho0 and Doxa1 cells; and Group D, genes more over-expressed in Doxa1.
Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.
None
Compound
View SamplesPre-mRNA splicing is functionally coupled to transcription, and genotoxic stresses can enhance alternative exon inclusion by affecting elongating RNA polymerase II. We report here that various genotoxic stress inducers, including camptothecin, inhibit the interaction between EWS, an RNA polymerase II-associated factor, and YB-1, a spliceosome-associated factor. This results in the cotranscriptional skipping of several exons of the MDM2 gene encoding the main p53 ubiquitin-ligase. This reversible exon skipping participates in the timely regulation of MDM2 expression, and may contribute to the accumulation of p53 during stress exposure and its rapid shut off when stress is removed. Finally, a splicing-sensitive microarray identified numerous exons that are skipped in response to camptothecin and EWS/YB-1 depletion. These data demonstrate genotoxic stress-induced alteration of the communication between the transcriptional and splicing machineries, resulting in widespread exon skipping and playing a central role in the genotoxic stress response.
Cotranscriptional exon skipping in the genotoxic stress response.
Specimen part, Cell line
View SamplesWe have generated over 80 million 32 nt reads generated from RNA samples isolated from the tip and base of a developing Mo17 leaf. A comparision of these data with the maize AGP resulted in the confirmation of approximately 88% of the maize filtered gene set Keywords: Transcriptome analysis Overall design: Examination of two different RNA samples from two different segments of a developing 3rd leaf
The B73 maize genome: complexity, diversity, and dynamics.
Specimen part, Subject
View SamplesAll above ground organs of higher plants are ultimately derived from shoot apical meristems (SAMs). The SAM exhibits distinctive structural organization, and monocot SAMs such as maize are comprised of two cell layers, a single cell layered tunica (L1) and a corpus (L2). Although recent research has revealed roles of these cell layers in the SAM, intra- and inter-cell-layer signaling networks involved in organ development remain largely unknown except for a few differentially expressed genes. Here, we used Illumnia technology to conduct RNA-seq of L1 and L2 cell layers in maize B73 maize shoot apical meristem. Overall design: Single sequencing library was constructed for L1 and L2 cell layer. Each library was sequenced using 2 lanes on a Solexa flow cell. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Subject
View SamplesHeterosis (hybrid vigor) refers to the superior performance of hybrid progeny relative to their parents. Although widely exploited in agriculture, the mechanisms responsible for heterosis are not well understood. As a monoecious organism, a given maize plant can be used as both male and female parents of crosses. Regardless of the cross direction, the maize inbred lines B73 and Mo17 produce hybrids that substantially out-perform their parents. These reciprocal hybrids differ phenotypically from each other despite having identical nuclear genomes. Consistent with these phenotypic observations, 30-50% of genes were differentially expressed between these reciprocal hybrids. An eQTL experiment conducted to better understand the regulation of gene expression in inbred and hybrid lines detected ~4,000 eQTL associations. The majority of these eQTL act in trans to regulate expression of genes on other chromosomes. Surprisingly, many of the trans-eQTL, when heterozygous, differentially regulated transcript accumulation in a manner consistent with gene expression in the hybrid being regulated exclusively by the paternally transmitted allele. The design of the eQTL experiment controlled for cytoplasmic and maternal effects, suggesting that widespread paternal genomic imprinting contributes to the regulation of gene expression in maize hybrids. Keywords: eQTL, parent-of-origin Overall design: GPL4521 - SAM1.2 (Reciprocal Hybrid Comparison): Six replications of B73xMo17 and Mo17xB73 were grown in growth chambers to tightly control environmental variation. Seeds from each genotype were taken from a single source (ear) for all six replications. Within each replication, genotypes were randomly assigned growth locations. Six healthy seedlings for each genotype and replication were harvested at two weeks of age. For each replication, B73xMo17 and Mo17xB73 were hybridized to the SAM1.2 microarray (GPL4521) using a randomized, alternate dye assignment. GPL3333 - SAM1.1 and GPL3538 - SAM3.0 (eQTL Experiment): Four biological replications of the RIL, B73xRIL, and Mo17xRIL cross-types were planted in growth chambers using seed from a single source for each genotype. Each RIL and its crosses onto B73 and Mo17 were planted using a split-plot design with RIL group (RIL and its cross onto B73 and Mo17) as the whole-plot treatment factor and cross-type (RIL, B73xRIL, and Mo17xRIL) as the split-plot treatment factor. The whole-plot portion of the experiment was designed as a randomized complete block design with four replications carried out on four separate occasions in the same environment. For the split-plot portion of the design, twelve seedlings of each RIL and its crosses were randomized within two adjacent flats in a growth chamber (six healthy seedlings per genotype were randomly chosen and pooled at harvest). For each replication, RIL, B73xRIL, and Mo17xRIL cross-types were hybridized to custom cDNA microarrays using a loop design such that each loop included all pairwise comparisons between the RIL and its crosses with B73 and Mo17. Four biological replications were hybridized to the SAM1.1 (GPL3333) array and two of the four biological replications were hybridized to SAM3.0 (GPL3538). RNA samples were alternately labeled to provide dye balance within each loop and replication. GPL8734 - Gene Expression between two maize reciprocal hybrids Heterosis refers to the enhanced agronomic performance of a hybrid relative to its (usually) inbred parents. We have previously documented widespread differences in gene expression in the B73xMo17 hybrid relative to its inbred parents B73 and Mo17 (Swanson, et al., 2006, PNAS). The reciprocal B73xMo17 and Mo17xB73 hybrids are both highly heterotic, but despite having identical nuclear genomes exhibit statistically significant differences in multiple traits. RNA-seq experiment was conducted to compare the gene expression globally between the two reciprocal hybrids. 1 samples from B73XMo17 and Mo17XB73 RNAs were extracted from a single replication of 14-day-old B73xMo17 and Mo17xB73 seedlings. RNAs were purified using DNaseI treatment followed by cleanup with the RNeasy Plant Mini Kit (Qiagen, Valencia, CA) as per manufacturer instructions. Sequencing library construction was completed using the Illumina mRNA-Seq sample preparation kit. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Specimen part
View Samples