ABSTRACT: Furin is a proprotein convertase (PC) responsible for proteolytic activation of a wide array of precursor proteins within the secretory pathway. It maps to the PRC1 locus, a type 2 diabetes susceptibility locus, yet its specific role in pancreatic β cells is largely unknown. The aim of this study was to determine the role of furin in glucose homeostasis. We show that furin is highly expressed in human islets, while PCs that potentially could provide redundancy are expressed at considerably lower levels. β cell-specific furin knockout (βfurKO) mice are glucose intolerant, due to smaller islets with lower insulin content and abnormal dense core secretory granule morphology. RNA expression analysis and differential proteomics on βfurKO islets revealed activation of Activating Transcription Factor 4 (ATF4), which was mediated by mammalian target of rapamycin C1 (mTORC1). βfurKO cells show impaired cleavage of the accessory V-ATPase subunit Ac45, and by blocking this pump in β cells the mTORC1 pathway is activated. Furthermore, βfurKO cells show lack of insulin receptor cleavage and impaired response to insulin. Taken together, these results suggest a model of mTORC1-ATF4 hyperactivation in β cells lacking furin, which causes β cell dysfunction.
Loss of <i>Furin</i> in β-Cells Induces an mTORC1-ATF4 Anabolic Pathway That Leads to β-Cell Dysfunction.
Sex, Age, Specimen part
View SamplesComparative analysis of gene expression profiles in newly developed housing systems is important to understand gene functions in chicken for adaptation and possible gene-environment interactions among layer lines. Therefore, the objective of this study was to characterize the molecular processes that are different among the two layer lines Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) using whole genome RNA expression profiles. Despite their approximately identical egg production performance these layer lines differ markedly in other phenotypic traits. The two layer lines were kept under the production environment of the newly developed small group housing system Eurovent German with two different group sizes and three tiers.
Differential gene expression from genome-wide microarray analyses distinguishes Lohmann Selected Leghorn and Lohmann Brown layers.
Specimen part
View SamplesTo address the functional role of KDM6A in the regulation of Rhox genes, male and female mouse ES cells were transfected with a mixture of three small interfering RNA duplexes, each of which targets a different region of Kdm6a mRNA. We found that Kdm6a knockdown in mouse ES cells caused a decrease in expression of a subset of Rhox genes, Rhox6 and 9. Furthermore, Rhox6 and 9 expression was decreased in female ES cells but not male ES cells indicating that KDM6A regulates Rhox gene expression in a sexually dimorphic manner.
Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
Specimen part, Cell line
View SamplesLncRNA H19X was silienced in dermal fibroblats of systemic sclerosis patients with antisense oligonuclotides. The hypothesis tested in the present study was that H19X is an important factor in the development of TGFb-driven fibrosis. Results provide important information about the role H19X in fibroblasts in particolar on extracellular matrix production and cell cycle regulation.
Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis.
Specimen part, Disease, Disease stage, Treatment
View SamplesIn both beef and dairy cattle, the majority of embryo loss occurs in the first 14-16 days following insemination. During this period, the embryo is completely dependent on its maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to embryo survival.
Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression.
Specimen part
View SamplesWe reported transcriptional characterization of Treg and Tconv cells from thymic, splenic, and visceral adipose tissue (VAT) of vTreg53 TCR transgenic mice and control littermates. We examined the effect of Foxp3 on splenic and VAT CD4+ T cell transcriptome. We profiled gene expression in a novel PPARg+ splenic Treg population. We uncovered that the characteristic phenotype of VAT Treg cells was acquired in two stages. Overall design: Gene expression profiles of thymic, splenic, VAT Treg, Tconv, and Foxp3-transduced Tconv cells from vTreg53 TCR transgenic and PPARg reporter mice.
TCR Transgenic Mice Reveal Stepwise, Multi-site Acquisition of the Distinctive Fat-Treg Phenotype.
Specimen part, Cell line, Subject
View SamplesWe report RNA sequencing data from tenocytes treated with IGF1. Tenocytes were obtained from the tail tendons of adult C57Bl/6 mice via collagenase digestion. Tenocytes were grown to 60% confluence, and then treated with 100ng/mL of recombinant IGF1 for a period of 0, 1, 2, 6, or 24 hours. Experiments were conducted in quadruplicate. RNA was isolated and prepared for RNA sequencing. Overall design: Differential expression of mRNAs were evaluated from tenocytes isolated from tail tendons of adult wild type C57Bl/6 mice that were treated with recombinant IGF1 for 0, 1, 2, 6, and 24 hours.
Insulin-like growth factor 1 signaling in tenocytes is required for adult tendon growth.
Specimen part, Cell line, Subject
View SamplesWith their genome sequenced, Anopheles gambiae mosquitoes now serve as a powerful tool for basic research in comparative, evolutionary and developmental biology. The knowledge generated by these studies is expected to reveal molecular targets for novel vector control and pathogen transmission blocking strategies. Comparisons of gene-expression profiles between adult male and nonblood-fed female Anopheles gambiae mosquitoes revealed that roughly 22% of the genes showed sex-dependent regulation. Blood-fed females switch the majority of their metabolism to blood digestion and egg formation within 3 h after the meal is ingested, in detriment to other activities such as flight and response to environment stimuli. Changes in gene expression are most evident during the first, second and third days after a blood meal, when as many as 50% of all genes showed significant variation in transcript accumulation. After laying the first cluster of eggs (between 72 and 96 h after the blood meal), mosquitoes return to a nongonotrophic stage, similar but not identical to that of 3-dayold nonblood-fed females. Ageing and/or the nutritional state of mosquitoes at 15 days after a blood meal is reflected by the down-regulation of 5% of all genes. A full description of the large number of genes regulated at each analysed time point and each biochemical pathway or biological processes in which they are involved is not possible within the scope of this contribution. Therefore, we present descriptions of groups of genes displaying major differences in transcript accumulation during the adult mosquito life. However, a publicly available searchable database (Anopheles gambiae Gene Expression Database at UC Irvine) has been made available so that detailed analyses of specific groups of genes based on their descriptions, functions or levels of gene expression variation can be performed by interested investigators according to their needs.
Genome-wide analysis of gene expression in adult Anopheles gambiae.
No sample metadata fields
View SamplesTo obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Overall design: Drosophila trained with an appetitive conditioning paradigm using Sucrose were collected prior to starvation, training, and 1 or 4 hours post-training, 5 to 6 replicates each, for RNA-Seq analysis of the fly heads with an Illumina HiSeq 2000.
Antimicrobial peptides modulate long-term memory.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A gene expression atlas of early craniofacial development.
Specimen part
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