This SuperSeries is composed of the SubSeries listed below.
Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Specimen part, Time
View SamplesWe have integrated dynamic RXRa binding, chromatin accessibility and promoter epigenetic status with the transcriptional activity inferred from RNA polymerase II mapping and transcription profiling. This demonstrated a temporal organization structure, in which early events are preferentially enriched for common GRNs, while cell fate specification is reflected by the activation of late programs in a cell-type specific manner. Furthermore, significant differences in cell lines' promoter status of genes associated with cell-line specific programs were inferred. Finally, a variety of transcription factors (TFs) playing a direct role in the signal transduction cascade downstream of the RXR/RAR initiated wiring were identified, several of them commonly regulated in both model systems, but in addition cell-type specific TF drivers were also identified.
Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Specimen part, Time
View SamplesHere we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction.
Sex, Age, Specimen part, Subject
View SamplesWe used microarrays to identify differentially expressed genes after DNA-damaging agent bleomycin (BLM) and/or immune inducer 2, 6-dichloroisonicotinic acid (INA) treatment. We focused on those genes that were synergistically induced by co-treatment (BLM+INA).
Salicylic acid activates DNA damage responses to potentiate plant immunity.
Specimen part, Treatment
View SamplesPurpose: The goals of this study are to compare transcriptome profiling (RNA-seq) resulting from a Mesp1Cre driven ablation of Hira in the heart at E11.5 and E12.5. Methods: RNA extraction was done in triplicate from Mesp1Cre;Hira-/fl and Mesp1Cre;Hira+/fl embryonic hearts at E11.5 and E12.5 using the QIAGEN RNeasy mini kit. RNAseq was processed by the ICH genomics facility, reads were aligned and normalised using BOWTIE and DEseq R package. Strand NGS 2.5 software was used to re-analyse the aligned files (.bam). By applying the Mann Whitney unpaired test, Benjamini Hochberg False discovery rate (FDR) and filtering the genes using adjusted p-value = 0.05 and absolute fold change = 1.5, 95 % of the results were identical to the DEseq package used by the UCL Genomics facility. Results: We identified 360 coding transcripts changed in the mutant hearts (Mann Whitney unpaired test, Benjamini Hochberg FDR, p = 0.05, FC = 1.5) with no trend towards up- or down-regulation of global transcription (48.8% down vs 51.2% up) at E12.5. Conclusions: This work analyses the role of HIRA in mouse cardiac development. It was found that Tnni2 is the most upregulated gene in the absence of Hira. qRT-PCR validation of 25 targets. Little (<5%) or no variation of fold change between RNAseq and qRT-PCR data were observed. Overall design: Cardiac mRNA profiles of 11-day and 12-day embryonic days Mesp1Cre control (Ctrl) and Mesp1Cre;Hira-/fl (mut) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
HIRA Is Required for Heart Development and Directly Regulates Tnni2 and Tnnt3.
Specimen part, Cell line, Subject
View SamplesWe analyzed samples from 770 male human subjects who are part of the METSIM study. Ethics Committee of the Northern Savo Hospital District approved the study. All participants gave written informed consent. The population-based cross-sectional METSIM study included 10 197 men, aged from 45 to 73 years, who were randomly selected from the population register of the Kuopio town in eastern Finland (population 95000). Every participant had a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio, including an interview on the history of previous diseases and current drug treatment and an evaluation of glucose tolerance and cardiovascular risk factors. After 12 h of fasting, a 2 h oral 75 g glucose tolerance test was performed and the blood samples were drawn at 0, 30 and 120 min. Plasma glucose was measured by enzymatic hexokinase photometric assay (Konelab Systems reagents; Thermo Fischer Scientific, Vantaa, Finland). Insulin was determined by immunoassay (ADVIA Centaur Insulin IRI no. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). Height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference (at the midpoint between the lateral iliac crest and lowest rib) and hip circumference (at the level of the trochanter major) were measured to the nearest 0.5 cm. Body composition was determined by bioelectrical impedance (RJL Systems) in subjects in the supine position.
Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Sex, Age, Specimen part
View SamplesAryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. Hitherto, indoleamine-2,3-dioxygenase 1 (IDO1) or tryptophan- 2, 3-dioxygenase (TDO2) are recognized as the main Trp-catabolizing enzymes (TCEs) responsible for the generation of AHR agonists. Here, the ability of the aromatic L-amino acid oxidase, interleukin 4 induced 1 (IL4I1), to activate the AHR was investigated using IL4I1 knockout CAS-1 glioblastoma cells.
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Cell line
View SamplesAnalysis of the effect of IL4I1 on gene expression of CD8 T-cells in CLL
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Sex
View SamplesIndole-3-pyruvate (I3P), an endogenous metabolite derived from tryptophan by gut microbiota and IL4I1 enzyme in humans can potentially activate the transcriptional activity of the Aryl Hydrocarbon receptor. Here we test this by stimulating AHR proficient U-87MG cells with I3P alone or in combination with the AHR antagonist SR1.
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Cell line
View SamplesTransformation of the Arabidopsis ATHB17 gene into maize results in the expression of a truncated protein (smaller by 113 amino acids) that functions as a dominant-negative regulator that can modify activity of endogenous maize HD-Zip II transcription factors. This RNASeq experiment indicates that the observed effects of ATHB17d113 on the maize ear inflorescence and ear transcriptome are very small. Expression of ATHB17delta113 protein in maize leads to changes in ear growth resulting in increased ear size at early reproductive stages and, potentially increased sink size. Overall design: Two ATHB17delta113 expressing events (Event 1 and Event 2) were compared to control plants (herein referred to as WT) in the context of Monsanto Elite Maize hybrid line NN6306. Three bioreps of both Ear inflorescence and Ear tissues were sampled for the WT and each of the two transgenic events.
Expression of a truncated ATHB17 protein in maize increases ear weight at silking.
Specimen part, Subject
View Samples