Based on the developmental origin of health of disease hypothesis, we previously showed that prenatal 70% maternal food restriction (FR30) predisposes the offspring to development of pathologies in adulthood. In the present study, we focused on the liver gene expression profile of standard and high fat (HF)-fed FR30 adult offspring.
No associated publication
Sex, Age, Specimen part
View SamplesBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological. We used transcriptomic analysis to investigate LXR pathway, and cholesterol metabolism in leukemic cells. Malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL), as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of ATP Binding Cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with three signaling pathways associated with leukemic cell survival, namely: NF-B activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor IL-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with an increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.
LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Specimen part, Subject
View SamplesMolecular mechanisms underlying terminal differentiation of B-cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here, we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B-cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels but followed by a committal step in which an S-phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity.
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
No sample metadata fields
View SamplesWe determined gene expression profiles which were induced in the chick chorio-allantoic membrane 24 h after application of recombinant human VEGF.
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
No sample metadata fields
View SamplesHuman pancreatic adenocarcinoma cells were grafted on the chick chorioallantoic membrane (CAM). Human and chicken GeneChips were used simultaneously to study gene regulation during PDAC cell invasion.
Netrin-1 mediates early events in pancreatic adenocarcinoma progression, acting on tumor and endothelial cells.
No sample metadata fields
View SamplesVaccine adjuvants enhance adaptive immunity to co-administered antigens. Whereas the modes of action are multiple, the activation of antigen-presenting cells (APC) like dendritic cells by adjuvants is a prerequisite. Detection of microbial signals by innate sensors like Toll-like receptors (TLR) is a major mechanism of APC activation. Most candidate or licensed vaccines assume that adjuvant activity of TLR agonists depends on direct effect on APCs. This study addressed whether TLR stimulation of non-hematopoietic cells could contribute to the adjuvant effect. Nasal administration of flagellin enhanced Tcell- and antibody-mediated immunity to co-administered antigens in a TLR5-dependent but inflammasome-independent manner. We found that lung radioresistant cells were sufficient to promote immunity, thereby suggesting that direct TLR5-mediated APC stimulation is dispensable to adjuvant activity. Consistent with this, radioresistant compartment is essential to stimulate the swift TLR5-dependent transcription. The transcriptional response was restricted to the epithelial compartment and was associated to the production of a narrow set of mediators including the chemokine CCL20, known to promote APC recruitment in mucosal tissues. Besides, flagellin was rapidly degraded in lower airways and was not transported into lung parenchyma or peripheral tissues. This study therefore suggests an unexpected mechanism for how TLR agonists act as adjuvant and how epithelium is instrumental to sense and integrate microbial signals to promote adaptive immunity. In conclusion, the immune-enhancing effect of adjuvants on epithelial cells can be harnessed for improving vaccines.
No associated publication
Specimen part, Treatment
View SamplesMurine embryonic fibroblasts were isolated from WT and DGAT1,DGAT2-KO (D1D2KO) animals. mRNA was isolated from cells untreated (UNDIFF) or treated (DIFF) according to standard differentiation protocol for adipocytes (Harris, C, et al. JLR 2011).
DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes.
Specimen part
View SamplesIn the present study, Sn expressed on primary pig macrophages was crosslinked with the anti-Sn monoclonal antibody 41D3 and the mRNA expression profiles were compared, using the Affymetrix microarray technology, to macrophages incubated with the irrelevant, isotype matched, monoclonal antibody 13D12
The transcriptome of porcine alveolar macrophages (PAM) after antibody-mediated crosslinking of sialoadhesin (Sn, Siglec-1)
Age, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine.
Specimen part
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