Multiple sclerosis (MS) is a neurodegenerative disease with a presumed autoimmune component. Expression profiling in immune cells can therefore be used in order to identify genes and pathways involved in MS pathogenesis.
Systematic review of genome-wide expression studies in multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sex, Specimen part, Time
View SamplesTo understand the temporal changes occurring in adipose tissue gene expression during a one-year weightloss intervention, adipose tissue biopsies were collected from 19 healthy obese individuals at three time points.
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sex, Specimen part, Time
View SamplesFITFATTWIN study identified from the FinnTwin16 Cohort, which is a population based, longitudinal study of Finnish twins born between October 1974 and December 1979. The participants had no chronic disease affecting the ability to exercise, no acute disease, and no drug or alcohol abuse.
iGEMS: an integrated model for identification of alternative exon usage events.
Age, Specimen part
View SamplesT follicular helper CD4 T cells (Tfh) provide requisite help to B cells in the germinal centers (GC) of lymphoid tissue. GC Tfh are identified by high expression of the chemokine receptor CXCR5 and the inhibitory molecule PD-1. Although more accessible, blood contains lower frequencies of CXCR5+ and PD-1+ cells that have been termed circulating Tfh (cTfh). However, it remains unclear whether GC Tfh exit lymphoid tissues and populate this cTfh pool. To examine exiting cells, we assessed the phenotype of Tfh present within the major conduit of efferent lymph from lymphoid tissues into blood, the human thoracic duct. Unlike blood, we consistently identified a CXCR5-Bright PD-1-Bright (CXCR5BrPD-1Br) Tfh population in thoracic duct lymph (TDL). These CXCR5BrPD-1Br TDL Tfh shared phenotypic and transcriptional similarities with GC Tfh. Moreover, components of the epigenetic profile of GC Tfh could be detected in CXCR5BrPD-1Br TDL Tfh, and the transcriptional imprint of this epigenetic signature was enriched in an activated cTfh subset known to contain vaccine-responding cells. Together with data showing shared TCR sequences between the CXCR5BrPD-1Br TDL Tfh and cTfh, these studies identify a population in TDL as a circulatory intermediate connecting the biology of Tfh in blood to Tfh in lymphoid tissue. Overall design: Transcriptional features of germinal center Tfh were detected in a population of Tfh in the efferent lymph of the human thoracic duct and can be traced to an activated subset of circulating Tfh in blood.
T follicular helper cells in human efferent lymph retain lymphoid characteristics.
Specimen part, Subject
View SamplesWhile the genome sequence of many animals is now complete, their transcriptomes are less well characterised. Both genome-scale tiling arrays and massively parallel sequencing now allow transcriptomes to be mapped at unprecedented depth. We used both technologies to map the C. elegans transcriptome across development. This unbiased overview can serve as a framework for assessing transcriptome changes in a mutant animal and we compared the wild-type data with that of animals that have lost the nonsense-mediated decay (NMD) pathway. Results We find that while the great majority of detectable transcripts map to known gene structures, over 5% of transcribed regions are novel, falling outside current gene annotations. We show that at least 40% of these are novel exons. We also used both technologies to assess isoform complexity and estimate that at least 17% of genes change their major isoform across development. Having mapped the wild-type transcriptome, we examined how this is perturbed in animals lacking nonsense -mediated decay (NMD). NMD prevents expression of prematurely truncated proteins by degrading transcripts containing premature termination codons (PTCs). We find that ~20% of all genes produce transcripts that appear to be targets for NMD. While most of these arise from splicing errors, NMD targets are also enriched for transcripts that contain short open reading frames upstream of the predicted translational start (uORFs). We find an intriguing relationship between the strength of Kozak consensus surrounding the true start codon and the degree to which these uORF containing transcripts are targeted by NMD, suggesting that translational efficiency may be coupled to transcript turnover via the NMD pathway for many transcripts. Conclusions We have generated a high-resolution map of the C. elegans transcriptome and have used it to identify transcripts that are endogenous targets of the NMD machinery. We find that these targets arise principally through splicing errors and suggest that splicing and NMD are highly interlinked processes.
High resolution transcriptome maps for wild-type and nonsense-mediated decay-defective Caenorhabditis elegans.
No sample metadata fields
View SamplesSequencing of a pool of 9 bulls of varying conception rate (CR) scores from -2.9 to 3.5.
Cryopreserved bovine spermatozoal transcript profile as revealed by high-throughput ribonucleic acid sequencing.
No sample metadata fields
View SamplesWe investigated the transcriptional effects of p63 binding by analyzing ME180 cells depleted for all p63 isoforms via expression of a small hairpin RNA (shRNA) targeting the p63 oligomerization domain.
Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.
Age
View SamplesRheumatoid arthritis (RA) leads to progressive destruction of articular structures. Despite recent progress in controlling inflammation and pain, little cartilage repair has yet been observed. This in vitro study aims to determine the role of chondrocytes in RA-related cartilage destruction and antirheumatic drug-related regenerative processes. Human chondrocytes were three-dimensionally cultured in alginate beads. To determine the RA-induced gene expression pattern, human chondrocytes were stimulated with supernatant of RA synovial fibroblasts (RASF) and normal donor synovial fibroblasts (NDSF), respectively. To examine antirheumatic drug response signatures, human chondrocytes were stimulated with supernatant of RASF that have been treated with disease-modifying antirheumatic drugs (DMARD; azathioprine, sodium aurothiomalate, chloroquine phosphate, methotrexate), non-steroidal anti-inflammatory drugs (NSAID; piroxicam, diclofenac) or steroidal anti-inflammatory drugs (SAID; methylprednisolone, prednisolone). Genome-wide expression profiling with oligonucleotide microarrays was used to determine differentially expressed genes. Real-time RT-PCR and ELISA were performed for validation of microarray data. Following antirheumatic treatment, microarray analysis disclosed a reverted expression of 94 RA-induced chondrocyte genes involved in inflammation/NF-B signalling, cytokine/chemokine activity, immune response, proliferation/differentiation and matrix remodelling. Hierarchical clustering analysis showed that treatment of RASF with the DMARD azathioprine, gold sodium thiomalate and methotrexate resulted in chondrocyte gene expression signatures that were closely related to the healthy pattern. Treatment with the SAID methylprednisolone and prednisolone strongly reverted the RA-related chondrocyte gene expression, in particular the expression of genes involved in inflammation/NF-B and cytokine/chemokine activity. The NSAID piroxicam and diclofenac and the DMARD chloroquine phosphate had only moderate to marginal effects. Pathway analysis determined major mechanisms of drug action, for example pathways of cytokine-cytokine receptor interaction, TGF-/TLR/Jak-STAT signalling and ECM-receptor interaction were targeted. This in vitro study provides a comprehensive molecular insight into the antirheumatic drug response signatures in human chondrocytes, thereby revealing potential molecular targets, pathways and mechanisms of drug action involved in chondrocyte regeneration. Thus, the present study may contribute to the development of novel therapeutic chondro-protective compounds and strategies.
Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration.
No sample metadata fields
View SamplesTo study the gene expression profile of salivary glands with varying degrees of inflammation in Sjogren's and non Sjogren's patients
Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: macrophage harbingers of disease severity.
Specimen part, Disease
View Samples