The aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients
Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients.
Disease
View SamplesThe translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.
The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.
Disease
View SamplesMyzus persicae (green peach aphid) feeding on Arabidopsis thaliana induces a defense response, quantified as reduced aphid progeny production, in infested leaves but not in other parts of the plant. Similarly, infiltration of aphid saliva into Arabidopsis leaves causes only a local increase in aphid resistance. Further characterization of the defense-eliciting salivary components indicates that Arabidopsis recognizes a proteinaceous elicitor with a size between 3 to 10 kD. Genetic analysis using well-characterized Arabidopsis mutant shows that saliva-induced resistance against M. persicae is independent of the known defense signaling pathways involving salicylic acid, jasmonate, and ethylene. Among 78 Arabidopsis genes that were induced by aphid saliva infiltration, 52 had been identified previously as aphid-induced, but few are responsive to the well-known plant defense signaling molecules salicylic acid and jasmonate. Quantitative PCR analysis confirms expression of saliva-induced genes. In particular, expression of a set of O-methyltransferases, which may be involved in the synthesis of aphid-repellent glucosinolates, was significantly up-regulated by both M. persicae feeding and treatment with aphid saliva. However, this did not correlate with increased production of 4-methoxyindol-3-ylmethylglucosinolate, suggesting that aphid salivary components trigger an Arabidopsis defense response that is independent of this aphid-deterrent glucosinolate.
Myzus persicae (green peach aphid) salivary components induce defence responses in Arabidopsis thaliana.
Specimen part, Treatment
View SamplesPlant respiration responses to elevated growth [CO2] are key uncertainties in predicting future crop and ecosystem function. In particular, the effects of elevated growth [CO2] on respiration over leaf development are poorly understood. This study tested the prediction that, due to greater whole-plant photoassimilate availability and growth, elevated [CO2] induces transcriptional reprogramming and a stimulation of nighttime respiration in leaf primordia, expanding leaves, and mature leaves of Arabidopsis thaliana. In primordia, elevated [CO2] altered transcript abundance, but not for genes encoding respiratory proteins. In expanding leaves, elevated [CO2] induced greater glucose content and transcript abundance for some respiratory genes, but did not alter respiratory CO2 efflux. In mature leaves, elevated [CO2] led to greater glucose, sucrose and starch content, plus greater transcript abundance for many components of the respiratory pathway, and greater respiratory CO2 efflux. Therefore, growth at elevated [CO2] stimulated dark respiration only after leaves transitioned from carbon sinks into carbon sources. This coincided with greater photoassimilate production by mature leaves under elevated [CO2] and peak respiratory transcriptional responses. It remains to be determined if biochemical and transcriptional responses to elevated [CO2] in primordial and expanding leaves are essential prerequisites for subsequent alterations of respiratory metabolism in mature leaves.
Developmental stage specificity of transcriptional, biochemical and CO2 efflux responses of leaf dark respiration to growth of Arabidopsis thaliana at elevated [CO2].
No sample metadata fields
View SamplesTranscriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Transcriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Age, Specimen part
View SamplesDiclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as model eukaryote to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. Especially pleiotropic drug resistance genes and genes under control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as well as zinc-responsive genes.
Involvement of the pleiotropic drug resistance response, protein kinase C signaling, and altered zinc homeostasis in resistance of Saccharomyces cerevisiae to diclofenac.
Treatment
View SamplesThe sensation of hunger after a period of fasting and the sensation of satiety after eating is crucial to behavioral regulation of food intake, but the biological mechanisms regulating these sensations are incompletely understood. We studied the behavioral and physiological adaptation to fasting in the vinegar fly (Drosophila melanogaster). Here we show that flies demonstrated increased behavioral attraction to food odor when food-deprived with no corresponding increase in sensitivity in the peripheral olfactory system. Flies increased their food intake transiently in the post-fasted state, but returned to a stable baseline feeding level within 24 hr after return to food. This modulation in feeding was accompanied by a significant increase in the size of the crop organ of the digestive system, suggesting that fasted flies responded both by increasing their food intake and storing reserve food in their crop. The post-fasting feeding response was observed in both male and female flies of diverse genetic backgrounds. Expression profiling of head, body, and chemosensory tissues by microarray analysis revealed several hundred genes that are regulated by feeding state, including 247 genes in the fly head. We performed RNA interference-mediated knockdown of, takeout, one of the genes strongly downregulated by fasting in multiple tissues. When takeout was knocked down in all neurons the post-fasting feeding response was abolished. These observations suggest that a coordinated transcriptional response to internal physiological state may regulate both ingestive behaviors and chemosensory perception of food
Post-fasting olfactory, transcriptional, and feeding responses in Drosophila.
Specimen part, Treatment, Time
View SamplesIn this randomised placebo-controlled trial, irritable bowel syndrome (IBS) patients were treated with faecal material from a healthy donor (n=8, allogenic FMT) or with their own faecal microbiota (n=8, autologous FMT). The faecal transplant was administered by whole colonoscopy into the caecum (30 g of stool in 150 ml sterile saline). Two weeks before the FMT (baseline) as well as two and eight weeks after the FMT, the participants underwent a sigmoidoscopy, and biopsies were collected at a standardised location (20-25 cm from the anal verge at the crossing with the arteria iliaca communis) from an uncleansed sigmoid. In patients treated with allogenic FMT, predominantly immune response-related genes sets were induced, with the strongest response two weeks after FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected.
Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.
Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Specimen part
View SamplesHumoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Specimen part, Subject
View Samples