Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion.
Disease, Subject
View SamplesAcute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion.
Age, Disease, Disease stage
View SamplesThe Cdk7/cyclin H/mnage--trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by hypertrophic pathways. Using cardiac-specific Cre, we ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally. However, fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and Western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1 failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1 was functionally defective, and PGC-1 likewise was deficient. PGC-1 was shown to interact with MAT1 and Cdk7, in co-precipitation assays. Thus, we demonstrate an unforeseen essential role for MAT1 in operation of the PGC-1 family of co-activators.
Ménage-à-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1.
No sample metadata fields
View SamplesMale fertility and testis function changes with age and so it was sought to determine if these changes are accompanied by changes in gene expression.
Aging results in differential regulation of DNA repair pathways in pachytene spermatocytes in the Brown Norway rat.
Specimen part
View SamplesThe root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays. Single root tip zones can be used for full transcriptome analysis; further, the root apex zones are functionally very distinct from each other. RNA-Seq provided novel information about the transcripts compared to the arrays. These data will help optimize transcriptome techniques for dealing with small, rare samples. Overall design: Arabidopsis thaliana var. Columbia (COL-0) seedlings were grown on sterile solid media plates containing 0.5 % phytagel. The plates were vertically placed in growth chambers with continuous light (80-100 µmol m -2) at a constant temperature of 19° C. Eight day old seedlings were harvested into RNA-later solution in a 50 mL centrifuge tubes and stored at -20 °C freezer. The root tips were dissected into zone-I: 0.5mm from the tip including the root cap and root division zones, and zone-II: 1.5mm sections including root elongation and root hair zone. Microarray and sequencing experiments were performed.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part, Subject
View SamplesStressors may have negative or positive effects in dependence of the dose (hormesis). We studied this phenomenon in Caenorhabditis elegans by applying weak or severe abiotic (cadmium, CdCl2) and/or biotic stress (different bacterial diets) during cultivation/breeding of the worms, and determining developmental speed or survival rates and performing transcriptome profiling and RT-qPCR analyses to explore the genetic basis of the detected phenotypic differences. This study showed that a bacterial diet resulting in higher levels of energy resources in the worms (E. coli OP50 feeding) or weak abiotic and biotic stress especially promote the resistance against severe abiotic or biotic stress and the age-specific survival rate of WT. Overall design: Five experimental conditions; mostly three replicates per experimental condition; four contrasts between test and control conditions functionally analyzed.
Bacterial diet and weak cadmium stress affect the survivability of <i>Caenorhabditis elegans</i> and its resistance to severe stress.
Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part
View SamplesThe root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part
View SamplesSpc1/ Spc1K49R was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Genome wide transcription profiling of the effects of overexpression of Spc1 and its kinase dead mutant in Schizosaccharomyces pombe.
No sample metadata fields
View SamplesThe assembly of neural circuits involves multiple sequential steps such as the specification of cell types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections. This intricate and often prolonged process is guided by elaborate genetic mechanisms that regulate each developmental event. Evidence from numerous systems suggests that each cell type, once specified, is endowed with a genetic program that directs its subsequent development. This cell intrinsic program unfolds in respond to, and is regulated by, extrinsic signals, including cell-cell and synaptic interactions. To a large extent, the execution of this genetic program is achieved by the expression of specific sets of genes that support distinct developmental processes. Therefore, a comprehensive analysis of the developmental progression of gene expression in synaptic partners of neurons may provide a basis for exploring the genetic mechanisms regulating circuit assembly.
Developmental Coordination of Gene Expression between Synaptic Partners During GABAergic Circuit Assembly in Cerebellar Cortex.
Sex, Specimen part
View Samples