The plasma protein FHR1 induces release of inflammatory cytokines IL-1ß, IL-6, IL-18 or TNFa from blood-derived human monocytes. RNA sequencing was performed from RNA of BSA- or FHR1-treated monocytes from 4 different donors. In response to FHR1, 522 monocytic genes were upregulated (gene ontology enrichment analysis), including 35 inflammation related genes, e.g. TNF. Also, G protein-coupled receptors such as EMR2/ADGRE2 were upregulated in response to FHR1. Overall design: Blood-derived monocytes were treated with BSA or FHR1, after 4h RNA was isolated. RNA of 4 donors were combined and sequenced.
Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies.
Specimen part, Treatment, Subject
View SamplesWe focused on how mica fine particle influences macrophage activities.
Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica.
Specimen part, Cell line
View SamplesTo investigate the role of ADAR1 in gastric carcinogenesis, RNA sequencing and small RNA sequencing were performed in AGS and MKN-45 cells with stable ADAR1 knock-down. Changed frequencies of editing and messenger RNA (mRNA) and microRNA (miRNA) expression were then identified by bioinformatic analyses. Overall design: mRNA and miRNA sequencing were performed before and after stable knockdown of ADAR1 in AGS and MKN-45 cell line
Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.
No sample metadata fields
View SamplesMacrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function.
Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells.
Specimen part
View SamplesSevere fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the WHO most dangerous pathogens, has 12-30% fatality rates with a characteristic thrombocytopenia syndrome. With a majority of clinically diagnosed SFTSV patients older than ~50 years, age is a critical risk factor for SFTSV morbidity and mortality. Here, we report an age-dependent ferret model of SFTSV infection and pathogenesis that fully recapitulates the clinical manifestations of human infections. While young adult ferrets (=2 years old) did not show any clinical symptoms and mortality, SFTSV-infected aged ferrets (=4 years old) demonstrated severe thrombocytopenia, reduced white blood cells, and high fever with 93% mortality rate. Moreover, significantly higher viral load was observed in aged ferrets. Transcriptome analysis of SFTSV-infected young ferrets revealed strong interferon-mediated anti-viral signaling, whereas inflammatory immune responses were markedly upregulated and persisted in aged ferrets. Thus, this immunocompetent age-dependent ferret model should be useful for anti-SFTSV therapy and vaccine development. Overall design: Two groups of young adults (20-24 months, =2Y) and aged ferrets (48-50 months), =4 Y) were inoculated via the IM route with 107.6 TCID50 of the SFTSV CB1/2014 strain. PBMCs were isolated at 2 and 4 dpi from each group of ferrets (n=3) by density gradient centrifugation using Ficoll-Paque Plus according to the manufacture's protocol.
Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis.
Specimen part, Subject
View SamplesBlood-retina barrier (BRB) formation and retinal angiogenesis depend on beta-catenin signaling induced by the ligand norrin (NDP), the receptor frizzled4 (FZD4), co-receptor LRP5, and the tetraspanin TSPAN12. Impaired NDP/FZD4 signaling causes familial exudative vitreoretinopathy (FEVR), which may lead to blindness. Endothelial-cell specific inactivation of the Tspan12 gene at P28 using a Cdh5-CreERT2 driver shows that TSPAN12 functions in ECs to promote vascular morphogenesis and BRB formation in developing mice, and BRB maintenance in adult mice. 12 month after Tspan12 inactivation and loss of BRB maintenance with massive IgG and albumin extravasation we observe complement activation, cystoid edema, and impaired beta-wave in electroretinograms. RNA-Seq 6 month after Tspan12 inactivation provides a detailed view on the transcriptional response, including activation of antibody effector systems (complement and Fc receptors), inflammation and microglia responses, extracellular matrix organization and remodeling, and other responses. Overall design: Endothelial cell-specific inactivation of floxed Tspan12 was induced at P28 using a Cdh5-CreERT2 driver and total retina RNA (ribodepleted) from 4 control or ECKO retinas (8 samples) was subjected to RNA-Seq 6 months later
Endothelial Cell-Specific Inactivation of TSPAN12 (Tetraspanin 12) Reveals Pathological Consequences of Barrier Defects in an Otherwise Intact Vasculature.
Specimen part, Cell line, Subject
View SamplesWe performed high throughput RNA sequencing at preadipocyte (D0) and differentiated adipocyte (D7) of primary brown preadipocyte and found that Kruppel-like factor 16 (KLF11) gene that was downregulated in D7 was a novel negative regulator of adipogenesis. Overall design: To explore global view of gene expression during adipogenesis, RNA-seq was performed in the primary cultured brown preadipocyte (D0) and brown adipocyte after 7 day differentiation (D7). Compared with D0, 6,668 genes were identified as 2 fold differentially expressed genes (DEGs) at D7 including 2,836-upregulated genes and 3,832 down-regulated genes.
RNA-Seq Analysis Reveals a Negative Role of KLF16 in Adipogenesis.
Specimen part, Cell line, Subject
View SamplesGPCR19 pathway has been implicated in regulating various inflammation. However, the exact mechanism of immune regulation by GPCR19 pathway has not been elucidated in detail.
Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice.
Sex, Specimen part
View SamplesPrenatal alcohol exposure can cause long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations found in FASD.
Ethanol-related alterations in gene expression patterns in the developing murine hippocampus.
Specimen part
View SamplesAcute Myeloid Leukemia AML is a cancer in which the process of normal cell hematopoietic differentiation is disrupted. Evidence exists that AML comprises a hierarchy with leukemic stem cells giving rise to more differentiated, but immature and functionally incompetent populations. The similarity of these AML subpopulations to normal stages of hematopoietic differentiation has not been dissected comprehensively at the transcriptional level. Here we introduce Normal Memory Analysis (NorMA), a data analysis method that extracts from omic data the remnants of the healthy normal-like phenotype. Applying NorMA to gene expression data from AML uncovered a wealth of information in the normal-like component of data: the normal hematopoietic memory of AML tumor cells. We found significant variation within the patient population, and we found strong association of this normal hematopoietic memory with survival. We found that undifferentiated NorMA phenotype has significantly worse survival than differentiated NorMA phenotype, showing that the NorMA classification of tumors captures a biologically meaningful stratification of patients, with highly significant survival association. Patients with NorMA phenotype in the undifferentiated Hematopoietic Stem Cell HSC stage had the worst survival, with median survival time under 6 months. We further found significant survival differences between tumor groups with differentiated NorMA phenotype, depending on their hematopoietic path: AML patients with NorMA phenotype in megakaryocyte-erythroid progenitor MEP stage had significantly better survival than those with NorMA phenotype in granulocyte-macrophage progenitor GMP stage. Thus NorMA produced a stratification of AML cohorts by differentiation stage, with significant outcome differences. It also provided clean molecular signatures for these stages. NorMA can be used in many other contexts, to explore for example the tumor cell of origin, or disease predisposition.
An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis.
Specimen part
View Samples