This SuperSeries is composed of the SubSeries listed below.
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesBackground: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesBackground: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesBackground: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesWhile activation of canonical NF-?B signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-?B pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin ß receptor (LTßR)- and FN14-dependent p52 nuclear translocation, but not TNFa receptor (TNFR)-mediated, canonical NF-?B p65 nuclear translocation. Chemoproteomics identified cyclin dependent kinase 12 (CDK12) as the target of 919278. CDK12 inhibition by 919278, THZ1, or siRNA knock down all affect similar global transcriptional changes and prevent LTßR and FN14-dependent MAP3K14 (NIK) mRNA induction and subsequent protein accumulation. In addition, 919278 and THZ1 treatment reduce RNA Pol II CTD phosphorylation. This powerful approach of coupling a phenotypic screen with chemoproteomics revealed a novel regulatory pathway of the non-canonical NF-?B pathway that could serve as a therapeutic target in autoimmunity and cancer. Overall design: There are TWEAK stimulated and unstimulated conditions, 4hr and 24hr time points. 7 treatments (DMSO, BIO0702697, BIO0919278, BIO032202, NTsiRNA, siRNAs523626, siRNAs523629) in duplicates. In total, 56 sample were sequenced and analyzed.
CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling.
Cell line, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.
Specimen part, Cell line, Treatment
View SamplesMucosal-associated invariant T (MAIT) cells are abundant in humans and recognize conserved bacterial antigens derived from riboflavin precursors, presented by the non-polymorphic MHC class I-like molecule MR1. Here, we show via transcriptomic analysis that human MAIT cells are remarkably oligoclonal in both blood and liver, display high inter-individual homology, and exhibit a restricted length CDR3ß domain of the TCRVß chain. We extend this analysis to a second sub-population of MAIT cells expressing a semi-invariant TCR conserved between individuals. Overall design: Study of CDR3 regions of TCRalpha and beta sequences
Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire.
No sample metadata fields
View SamplesWe have determined that sustained expression of EBF suppresses alternate lineage genes independently of Pax5.
Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5.
No sample metadata fields
View SamplesThe role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution. Overall design: We carried out RNA-sequencing (RNA-seq) of human neural progenitors cells. For the RNA-seq, 5 indipendent replicates were used for the neural progenitor cells. Primary human neural progenitor cultures were derived from mid-gestation fetal brain. Cells were transduced with a lentivirus containing a specific shRNA to ELAVL2 or a control shRNA. Cells were differentiated into neurons for 4 weeks and then harvested.
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.
No sample metadata fields
View SamplesOur findings demonstrate that CDCP1 is a novel modulator of HER2 signalling, and a biomarker for the stratification of breast cancer patients with poor prognosis
Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.
Cell line
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