This dataset consists of single-cell RNA-seq (Drop-seq) data from thymi of day 14.5 mouse embryos. The sample includes the whole thymus, including mesenchyme, endothelium, epithelium, thymocytes, and other lymphocytes. The mouse is a Rag2-/- knockout. Overall design: 1 sample
Inferring population dynamics from single-cell RNA-sequencing time series data.
Specimen part, Subject
View SamplesGender dimorphism exists in the physiological response to diet and other environmental factors. Trans-hydrogenated fatty acid (TFA) intake is associated with an increase in coronary heart disease (CHD), and gender differences in the incidence of CHD are well documented. Neonatal administration of Monosodium Glutamate (MSG) causes stunted heart growth and hypoplasticity; and gender dimorphism at the growth hormone axis has been demonstrated in MSG-treated rodents. The identification of gender dimorphism in cardiac nutrigenomics may provide the basis for gender-specific medicine in the future.
Sex-dimorphism in cardiac nutrigenomics: effect of trans fat and/or monosodium glutamate consumption.
Sex, Specimen part
View SamplesMissense mutations in coding region of PDX1 predispose to type-2 diabetes mellitus as well as cause MODY through largely unexplored mechanisms. Here, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying heterozygous missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1P33T/+, PDX1C18R/+ mutations and engineered isogenic cell lines carrying homozygous PDX1P33T/P33T, PDX1C18R/C18R mutations and a heterozygous PDX1 loss-of-function mutation (PDX1+/-). Using an in vitro ß-cell differentiation protocol, we demonstrated that both PDX1P33T/+, PDX1C18R/+ and PDX1P33T/P33T, PDX1C18R/C18R mutations impair ß-cell differentiation and function. Furthermore, PDX1+/- and PDX1P33T/P33T mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1P33T/+ and PDX1P33T/P33T mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NEURONATIN, both involved in insulin synthesis and secretion. Our results reveal mechanistic details of how diabetes-associated PDX1 point mutations impair human pancreatic endocrine lineage formation and ß-cell function and contribute to pre-disposition for diabetes. Overall design: We performed RNA-seq of control and isogenic PDX1 mutant cell lines at PP stage
Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Specimen part
View SamplesObjective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing -cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far.
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Specimen part
View SamplesP. falciparum NF54 proliferates under micro-aerophilic conditions in an environment of 3% O2, 4% CO2, 93% N2. This strain was gradually adapted to proliferate under standard tissue culture conditions of 5% CO2/95% air (~19% O2) to generate P. falciparum HOX. We compared global gene expression profiles of the two strains to identify differences, if any.
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
No sample metadata fields
View SamplesInsulin-dependent diabetes is a complex multifactorial disorder characterized by
Identification of proliferative and mature β-cells in the islets of Langerhans.
Sex, Specimen part
View SamplesBACKGROUND: Cadmium is implicated in prostate carcinogenesis, but its oncogenic action remains unclear.
Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor.
Sex
View SamplesNon-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat. Overall design: RNA-seq on Drosophila head samples fed control and sucralose diet
Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.
Specimen part, Cell line, Subject
View SamplesPiriformospora indica, an endophytic fungus of Sebacinales, colonizes the roots of many plant species including Arabidopsis thaliana. The symbiotic interaction promotes plant per-formance, growth and resistance/tolerance against abiotic and biotic stress. We demonstrate that exudated compounds from the fungus activate stress and defense responses in the Arabidopsis roots and shoots before the two partners are in physical contact. They induce stomata closure, stimulate reactive oxygen species (ROS) production, stress-related phytohormone accumulation and activate defense and stress genes in the roots and/or shoots. Once a physical contact is established, the stomata re-open, ROS and phytohormone levels decline, and the gene expression pattern indicates a shift from defense to mutualistic interaction.
The interaction of Arabidopsis with Piriformospora indica shifts from initial transient stress induced by fungus-released chemical mediators to a mutualistic interaction after physical contact of the two symbionts.
Age, Specimen part
View Samples