Gene expression of hepatic stellate cells exposed to fetal bovine serum (FBS)
Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice.
Sex, Specimen part
View SamplesNeutrophils represent a fundamental mechanism of antimicrobial resistance and inflammation 1. Moreover, neutrophils have emerged as important players in the activation, orchestration and regulation of adaptive immune responses2,3. Neutrophils are a component of the tumor microenvironment (TME) and have been prevalently shown to promote progression 4-6. On the other hand, unleashed neutrophilic effectors have also been reported to mediate anti-cancer resistance7-11. Antibody-mediated depletion used to investigate the role of neutrophils in tumor progression suffers from limitations, including duration, specificity and perturbation of the system12. We therefore used a genetic approach to investigate the role of neutrophils in primary 3-methylcholanthrene (3-MCA)-induced sarcomagenesis. Neutrophils were found to play an essential role in resistance against primary carcinogenesis by driving an interferon-? dependent type 1 immune response. Neutrophil-dependent macrophage production of IL-12p70 led to type 1 polarization of CD4- CD8- unconventional aß T cells (UTCaß) in the TME. Single cell RNAseq analysis and in vivo evidence from two preclinical sarcoma models highlight the antitumor potential of a UTCaß subset. In the TCGA cohort of human undifferentiated pleomorphic sarcomas (UPS), unlike other sarcomas, granulocyte-colony stimulating factor receptor (CSF3R) expression and a neutrophil signature were associated with better outcome and with a type 1 immune response. The positive association between high neutrophil infiltration and improved clinical outcome was confirmed in an independent UPS cohort by immunohistochemistry. Thus, neutrophils, by driving a type 1 immune response and polarization of UTCaß, mediate resistance against murine and human sarcomas. Overall design: two experimental conditions, two biological replicates for each condition
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Specimen part, Subject
View SamplesThe aim of this study consists in detecting genes regulated by Meis2 in the murine cochlea
Meis2 Is Required for Inner Ear Formation and Proper Morphogenesis of the Cochlea.
Specimen part
View SamplesChronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B lymphocytes in peripheral blood, lymphoid organs and BM. The main feature of the disease is accumulation of the malignant cells due to decreased apoptosis. CD84 belongs to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors, and has an unknown function in CLL cells. Here, we show that the expression of CD84 is significantly elevated from the early stages of the disease, and is regulated by macrophage migration inhibitory factor (MIF) and its receptor, CD74. Activation of cell surface CD84 initiates a signaling cascade that enhances CLL cell survival. Both immune-mediated neutralization or blockade of CD84 induce cell death in vitro and in vivo. In addition, analysis of samples derived from an on-going clinical trial, in which human subjects were treated with humanized anti-CD74 milatuzumab shows a decrease in CD84 mRNA levels milatuzumab-treated cells. This downregulation was correlated with reduction of Bcl-2 and Mcl-1 message. Thus, our data show that overexpression of CD84 in CLL is an important survival mechanism that appears to be an early event in the pathogenesis of the disease. These findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.
CD84 is a survival receptor for CLL cells.
Disease
View SamplesUnderstanding how developmental and environmental signals are integrated to produce specific responses is one of the main challenges of modern biology. Hormones and, most importantly, interactions between different hormones serve as crucial regulators of plant growth and development, playing central roles in the coordination of internal developmental processes with the environment. Herein, a combination of physiological, genetic, cellular, and whole-genome expression profiling approaches has been employed to investigate the mechanisms of interaction between two key plant hormones, ethylene and auxin.
Multilevel interactions between ethylene and auxin in Arabidopsis roots.
No sample metadata fields
View SamplesACC Synthase (ACS) is the key regulatory enzyme in the ethylene biosynthesis in plants. It catalyzes the conversion of s-adenosylmethionine (SAM) to 1-aminocyclopropane-1-carboxylic acid (ACC), the precursor of ethylene. Arabidopsis has nine ACS genes. The goal of the project is to inactivate each gene by insertional mutagenesis and amiRNA technology and eventually construct a null ACS mutant. We have been recently able to achieve this goal. Furthermore, we wanted to know how inactivation of individual ACS genes affects global gene expression.
A combinatorial interplay among the 1-aminocyclopropane-1-carboxylate isoforms regulates ethylene biosynthesis in Arabidopsis thaliana.
No sample metadata fields
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View SamplesWild-type and mouse mutants for FGF3, FGF10 and FGF3/FGF10 double mutants at embryonic day E10 were analysed by microarrays for downregulated genes. A tissue sample corresponding to an area containing the otic vesicle and surrounding mesenchyme and neighboring hindbrain were isolated from E10 embryos (See Figure 3A of manuscript). Five samples were pooled for RNA preparation. Samples were isolated from wild-type, FGF3, FGF10 and FGF3/FGF10 double mutants. Two RNA samples for each genotype were generated (corresponding to 8 tissue samples). RNA was labeled and hybridized with Affymetrix U74A V2 arrays.
FGF signalling controls expression of vomeronasal receptors during embryogenesis.
Age, Specimen part, Disease, Disease stage
View SamplesWe generated a gene replacement allele of the E-cadherin locus that express an N-cadherin-GFP fusion in ES cells. Expression profiles of homozygous and heterozygous knock-in ES cells were analyzed in comparison to wt ES cells.
Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency.
No sample metadata fields
View SamplesPurpose: The goal of this study is to compare the transcriptome profilling (RNA-seq) of inflorescences infected with tobacco ratle virus (TRV) to mock inoculated inflorescences (negative controls), in Arabidopsis plants Methods: Inflorescences of systemically TRV infected or mock-inoculated plants were collected from more than 40 independent Arabidopsis plants, at 14 days post-inoculation (dpi). TRV and mock mRNA profiles were generated by deep sequencing by Illumina HiSeq 2000. The sequence reads that passed quality filters (SOAPnuke) were analysed by Burrows-Wheeler (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Genes and isoforms were quantified by RSEM sofware package. qRT-PCR validation was performed using TaqMan and SYBR Green assays. Results: Here we report a significant repression of DNA methylation genes in inflorescences of Arabidopsis plants infected with Tobacco rattle virus (TRV) that coincides with dynamic changes in methylation at the whole genome level. Arabidopsis mutants deficient in DNA methylation were more resistant to this virus in early colonized tissues but more susceptible at later time points of infection, indicating that DNA methylation was critical to control both proliferation and antiviral defense. We found that TRV interference with DNA methylation leads to changes in the methylation and trancriptional status of transposable elements (TEs), including TEs located in the promoter of disease resistance genes that were significantly repressed in plants exposed to TRV. Activation of both TEs and their nearby disease resistance genes was altered in a range of hypo- and hyper-methylated Arabidopsis mutants, indicating that perturbations in DNA methylation contributes to modulate their expression in infected plants. Conclussion: Our study showed that TRV interferes with DNA methylation to alter the transcriptional silencing of TEs, which in turn compromises the expression of neighboring disease resistance genes. Overall design: TRV and mock mRNA profiles were generated from Arabidopsis inflorescences by deep sequencing with Illumina HiSeq 2000.
Crosstalk between epigenetic silencing and infection by tobacco rattle virus in Arabidopsis.
Specimen part, Subject
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