Stem cell differentiation is known to involve changes in RNA expression, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of embryonic stem cells (ESCs) into embyroid bodies (EBs) by integrating conventional transcriptome analysis with global assessment of ribosome loading. Differentiation was accompanied by an anabolic switch, characterized by global increases in transcript abundance, polysome content, protein synthesis rates and protein content. Furthermore, 78% of expressed transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Elevated protein synthesis was accompanied by enhanced phosphorylation of eIF-4E binding protein, suggesting regulation by the mTOR pathway.
A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation.
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View SamplesComparison between two vegetative stages of the soybean cultivar BR16: 20 and 80 days after germination (DAG) Overall design: Examination of 2 vegetative stages: 20 and 80 DAGs
Revisiting the Soybean GmNAC Superfamily.
Age, Specimen part, Subject
View SamplesAlthough human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the metabolic substrate switch from glucose to fatty acids. We hypothesized that fatty acid supplementation would enhance hPSC-CM maturation. Fatty acid treatment induces cardiomyocyte hypertrophy and significantly increases cardiomyocyte force production. The improvement in force generation is accompanied by enhanced calcium transient peak height and kinetics, and by increased action potential upstroke velocity. Fatty acids enhance mitochondrial respiratory reserve capacity. RNA sequencing showed fatty acid treatment upregulates genes involved in fatty acid ß-oxidation and downregulates genes in lipid synthesis. Signal pathway analyses reveal that fatty acid treatment results in phosphorylation of multiple intracellular kinases. Thus, fatty acids increase human cardiomyocyte hypertrophy, force generation, calcium dynamics, action potential upstroke velocity, and oxidative capacity. This enhanced maturation should facilitate hPSC-CMs usage for cell therapy, disease modeling, and drug/toxicity screens. Overall design: We did RNA-seq of hPSC-CM culture in control and fatty acid media, with two biological replicates per condition
Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells.
Specimen part, Subject
View SamplesObjective: To study the physiological role of eosinophils in the GI tract and lung under homeostatic conditions,
The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia.
Specimen part
View SamplesAcute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups. Overall design: Total healthy bone marrow was sorted to isolate distinct cell populations. RNA-Seq analysis was performed on sorted cells to determine gene expression profile of healthy bona marrow subpopulations.
Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets.
Specimen part, Subject
View SamplesThe eosinophil transcriptome analysis indicated a robust transcription change in eosinophils following allergen challenge in the lung.
Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils.
Specimen part
View SamplesIntestinal macrophages rely on the constant replenishment by bone marrow derived Ly6Chigh monocytes in the adult organism. The developmental path from monocytes towards intestinal macrophages locally in the tissue is defined by the loss of Ly6C and acquisition of MHCII and CX3CR1 expression. We used microarray analysis to further characterise this local differentiation process.
Tissue-specific differentiation of colonic macrophages requires TGFβ receptor-mediated signaling.
Sex, Specimen part
View SamplesThe methyltransferase G9a was found to play a role in the disease progression of a murine model of AML.
The methyltransferase G9a regulates HoxA9-dependent transcription in AML.
Cell line
View SamplesWe analysed the transcriptome of different HSC-enriched subpopulations of cells sorted from human umbilical cord blood and isolated from several individuals with different genetic backgrounds. We aim at identifying new cell surface markers associated with human HSC and downstream mature hematopoietic cell activity. Overall design: RNA-seq of CD34+CD45RA- cord blood cells from 17 non-pooled individuals.
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Specimen part, Subject
View SamplesThe goal of the study was to identify genes that are directly or indirectly coregulated by the AhR pathway in primary human AML cells. Patient AML cells were treated for 16 hours with the two indirubin derivatives 6-bromoindirubin-3''oxime (BIO), 1-Methyl-6-bromoindirubin-3''oxime (MeBIO), the AHR-antagonist SR1 (StemReginin1), combinations of BIO+SR1 and MeBIO+SR1 or DMSO alone at indicated concentrations prior to RNA extraction for sequencing. Overall design: RNA-Seq performed on 5 primary AML samples fresh (t0) and after exposure to AhR-agonists (2), -antagonist (1), and DMSO Contributor: Leucegene Project, IRIC
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Specimen part, Subject
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