Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN- in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity
Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity.
Sex, Specimen part
View SamplesGene expression profiling of B-cells from a model differentiation series: from Nave B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.
In vitro generation of long-lived human plasma cells.
Sex, Specimen part
View SamplesThe goal of this RNA-Seq analysis was to identify genes differentially expressed in a C. elegans strain overexpressing HSP-90 in the neurons compared to control (N2) animals. C. elegans overexpressing HSP-90 protein in the neurons activate transcellular chaperone signalling that enhances organismal proteostasis. This study aimed to identify components of the signalling pathway responsible for this effect. Overall design: Gene expression profile of L4 C. elegans wild type (N2) animals compared to L4 C. elegans overexpressing HSP-90::GFP in the neurons, using a neuron-specific promoter (F25B3.3p), grown at 20C. 3 replicates of each sample.
A PQM-1-Mediated Response Triggers Transcellular Chaperone Signaling and Regulates Organismal Proteostasis.
Cell line, Subject
View SamplesCombinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3
Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
No sample metadata fields
View SamplesAffymetrix arrays measuring gene expression in 3 Drosophila Insensitive mutant embryos and 3 Drosophila wt mutant embryos
The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
No sample metadata fields
View SamplesRNA-binding proteins (RBPs) are critical regulators of gene expression and elucidating the interactions of RBPs with their RNA targets is necessary to understand how combinations of RBPs control transcriptome expression. The Quaking-related (QR) sub-family of STAR domain RBPs includes developmental regulators and tumor suppressors such as C. elegans GLD-1, which functions as a master regulator of germ line development. To understand how GLD-1 interacts with the transcriptome, we identified GLD-1 associated mRNAs by a ribonomic approach. The scale of GLD-1 mRNA interactions allowed us to determine rules governing GLD-1 target selection and to derive a predictive model where GLD-1 association with mRNA is based on the number and strength of 7-mer GLD-1 binding elements (GBEs) within UTRs. GLD-1/mRNA interactions were quantified, and predictions were verified both in vitro and in live animals, including by transplantation experiments where weak and strong GBEs imposed translational repression of increasing strength on a non-target mRNA.Importantly, this study provides a unique quantitative picture of how an RBP interacts with its mRNA targets. As combinatorial regulation by multiple RBPs is thought to regulate gene expression, quantification of RBP/mRNA interactions should be a way to predict and potentially modify biological outcomes of complex posttranscriptional regulatory networks, and our analysis suggests that such an approach is possible.
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Specimen part
View SamplesThe response to nitrogen starvation was studied in S. pombe. This experiment contains expression data from Affymetrix Yeast 2.0 arrays.
Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes.
No sample metadata fields
View SamplesLong-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View Samples