The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-?) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-? bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-?/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-?/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system. Overall design: polyA RNA profiling of Neural Stem/Progenitor cells (NPCs) cultured in basal/Th1/Th2 conditions, of Exosomes derived from NPCs cultured in basal/Th1/Th2 conditions and of EVs derived from NPCs cultured in Basal/Th1/Th2 conditions. Total RNA was purified using Trizol. Purity and integrity were confirmed by BioAnalyser (Agilent). Paired End library construction and poly-A selection were performed by EASIH (The Eastern Sequence and Informatics Hub, University of Cambridge, Cambridge) according to the Illumina standard protocol. Sequencing was performed by EASIH using Illumina GAII.
Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.
Specimen part, Cell line, Subject
View SamplesThe aim of this study is to analyze the transcriptome of epithelial (CD326+ enriched) and immune (CD45+ enriched) fraction in Celiac Disease and controls to find differentially expressed genes.
The methylome of the celiac intestinal epithelium harbours genotype-independent alterations in the HLA region.
Sex, Age, Specimen part, Disease
View SamplesCamptothecin (CPT) is a plant alkaloid that specifically binds topoisomerase I (Topo I) inhibiting its activity and inducing double stranded breaks in the DNA, activating the genotoxic cell responses, and ultimately, it might trigger programmed cell death (PCD). We used microarrays to detail the changes in gene expression during as a consequence of CPT treatment in maize immature embryos. In four independent experiments immature embryos were plated on MS medium supplemented with 50 uM CPT and incubated during three days. Untreated embryos incubated on MS medium were used as controls.
Transcriptomic and proteomic profiling of maize embryos exposed to camptothecin.
Specimen part, Compound
View SamplesThis study aims to investigate the role of microRNA-30c on hepatic and metabolic gene expression and physiology Overall design: For this experiment, we used male C57BL/6 mice. At an age of 8 weeks, we started them on Western diet for one month and then injected them with either PBS or increasing dose of Scr or miR-30c mimic (2.5, 5.0, and 7.5 mg/kg) for 6 weeks. Liver from these mice were harvested and flash frozen. RNA from the livers of these mice were extracted and RNA-seq was performed.
MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.
No sample metadata fields
View SamplesYoung adult fer-15;fem-1 Caenorhabditis elegans were infected with Staphylococcus aureus for 8 h to determine the transcriptional host response to Staphylococcus aureus. Analysis of differential gene expression in C. elegans young adults exposed to two different bacteria: E. coli strain OP50 (control), wild-type Staphylococcus aureus RN6390. Samples were analyzed at 8 hours after exposure to the different bacteria. These studies identified C. elegans genes induced by pathogen infection.
Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus.
Disease, Disease stage
View SamplesWe report the profiling of induced mRNA transcripts in two C. elegan replicate populations -- WT (N2) and mutant strain with deficient HLH30. Both strains were fed either OP50 strain of e-coli (normal feed) or S. aureus Overall design: Examination of infected versus uninfected wildtype and mutant lawns of animals
Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes.
Subject
View SamplesHuman mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DC) and monocytes, but their identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we clearly delineated monocytes from conventional DC2 (cDC2), identifying new markers including CD88/CD89 for monocytes and HLA-DQ/Fc?RI? for cDC2, allowing their unambiguous characterization in blood and tissues. We also show that cDC2 can be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163 and CD14 expression, including a unique subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3. These inflammatory DC3 were expanded in systemic lupus erythematosus patients, correlating with disease activity. Unravelling the heterogeneity of DC sub-populations in health and disease paves the way for specific DC subset-targeting therapies. Overall design: Indexed single cell RNAseq (scRNAseq) of human peripheral blood dendritic cells and monocytes
Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.
Specimen part, Subject
View SamplesAnalysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674).
Discovery of potent broad spectrum antivirals derived from marine actinobacteria.
Specimen part
View SamplesAnalysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with novel indole-2-carboxamide antivirals 205432 or 206381.
Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.
Specimen part, Treatment
View SamplesDendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the dendritic cell precursors within the peripheral blood.
Mapping the human DC lineage through the integration of high-dimensional techniques.
Specimen part, Subject
View Samples