Hematopoietic progenitor and stem cells from bone marrow have been sorted by FACS (LSK, Lineage -, Sca1 + and cKit +) and co-culture during 18h without cytokines with or without extracellular vesicles (EV) secreted by AFT stromal cells.
Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells.
Specimen part
View SamplesExtracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T cell lymphoma, graft versus host disease and allografted organ rejection. Its clinical and experimental efficacy in both cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the dendritic antigen presenting cell (DC) differentiation pathway, as determined by expression of relevant genes. The resulting DC are capable of processing and presentation of exogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of co-stimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome indicates that activation or suppression of more than 3500 genes produces a reproducible distinctive molecular signature. Pathway analysis suggests that DC maturation may be triggered by transient adherence of passaged monocytes to plasma proteins coating the ECP plastic ultraviolet exposure plate. Co-incubation with lymphocytes, simultaneously induced by ECP to undergo apoptosis, may accelerate conversion of monocytes to DC. The efficiency with which ECP induces new functional DC supports the possibility that these cells participate prominently in the clinical successes of the treatment. ECP may offer a practical source of DC for use in a spectrum of immunotherapeutic trials.
Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.
Disease, Disease stage
View SamplesSmall RNAs (sRNA) that act by base pairing with trans-encoded mRNAs modulate metabolism in response to a variety of environmental stimuli. Here, we describe an Hfq-binding sRNA (FnrS) whose expression is induced upon a shift from aerobic to anaerobic conditions and which acts to down regulate the levels of a variety of mRNAs encoding metabolic enzymes. Anaerobic induction in minimal medium depends strongly on FNR but is also affected by ArcA and CRP. Whole genome expression analysis showed that the levels of at least 32 mRNAs are down regulated upon FnrS overexpression, 15 of which are predicted to base pair with FnrS by TargetRNA. The sRNA is highly conserved across its entire length in numerous enterobacteria, and mutation analysis revealed that two separate regions of FnrS base pair with different sets of target mRNAs. The majority of the target genes previously reported to be down regulated in an FNR-dependent manner lack recognizable FNR binding sites. We thus suggest that FnrS extends the FNR regulon and increases the efficiency of anaerobic metabolism by repressing the synthesis of enzymes that are not needed under these conditions.
Reprogramming of anaerobic metabolism by the FnrS small RNA.
No sample metadata fields
View SamplesTo better understand the scale of gene expression changes that occur during the formation of mature adipocytes from preadipocytes, we compared and characterised the transcriptome profile of mesenchymal stromal cells derived from human adipose tissue, otherwise known as adipose-derived stromal cells (ASCs), undergoing adipocyte differentiation on day 1, 7, 14 and 21 (representing the early to late stage process of adipogenesis). Microarray technique was systematically employed to study gene expression in adipose-derived stromal cells during adipogenic differentiation over a 21 day period to identify genes that are important in driving adipogenesis in humans.
Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation.
Sex, Age, Specimen part, Subject
View SamplesHMF and furfural were pulse added to xylose-utilizing Saccharomyces cerevisiae during either the glucose consumption phase or the xylose consumption phase. Transcriptome samples were collected before and one hour after pulsing of inhibitors.
Pulsed addition of HMF and furfural to batch-grown xylose-utilizing Saccharomyces cerevisiae results in different physiological responses in glucose and xylose consumption phase.
Treatment
View SamplesMutations of -catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However, the target genes of CTNNB1 have not yet been identified in adrenocortical tumors.
Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.
Specimen part
View SamplesLesions of chronic idiopathic urticaria (CIU) showed significant up-regulation of 506 genes and reduced expression of 51 genes.
Gene expression profiles in chronic idiopathic (spontaneous) urticaria.
Specimen part, Subject
View SamplesMalignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
Epigenetic silencing of novel tumor suppressors in malignant melanoma.
No sample metadata fields
View SamplesDendritic cells are the initiators of the adaptive immune response, therefore its gene expression allow us to predict the responses to vaccination. We used bone marrow derived dendritic cells (BMDC) to analyze the gene expression that result from the exposure to adjuvants. We use model antigen OVA and cyclic di-AMP (CDA) as an adjuvant in order to characterize the genes involved in the activation of dendritic cells by CDA alone or when the antigen is present.
Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.
Treatment, Time
View SamplesVariable strengths of T cell receptor (TCR) signaling can produce divergent outcomes for T cell development and function. The mechanisms leading to different outcomes are incompletely understood, but may include distinct activation thresholds for different transcription factors as well as distinct sensitivities among target genes to transcription factors. IRF4 is one transcription factor implicated in responses to variable TCR signal strength. IRF4 expression increases uniformly with increasing TCR signal strength (i.e., analog), but it is unclear how IRF4 induced distinct genes at different levels, rather than different amounts of the same genes. Here, we analyzed global gene expression in TH2 cells and used ChIP-seq to define the relationship between TCR signal strength, enhancer occupancy and transcriptional activity for BATF/IRF4-dependent genes. We show that enhancers exhibit a spectrum of affinity for the BATF/IRF4 ternary complex mediate graded responsiveness of individual genes to increasing TCR signal strength. Differential gene induction by BATF and IRF4 occurs through interaction with enhancer elements of different affinity for BATF/IRF4 complexes. The increased resolution of factor binding site identified using ChIP-exo allowed the identification of a novel AICE2 motif binding BATF/IRF4 with higher affinity and that this may explain the protective role of a single nucleotide polymorphism in the CTLA-4 locus known to decrease the incidence of autoimmune diseases.
Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex.
Specimen part
View Samples