OGR1 is a pH sensing G protein-coupled receptor involved in intestinal homeostasis and inflammation. Up-regulation of genes, mediated by OGR1, in response to extracellular acidification were enriched for inflammation, immune response, actin cytoskeleton and cell adhesion pathways.
G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal Inflammation.
Specimen part, Treatment
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 SamplesRegulatory T cells (Tregs) are key brakes on the VAT inflammation that regulates local and systemic metabolic tenor. The cytokine, IL-33, expands and sustains the unique Treg population residing within VAT. Making use of single-cell RNA sequencing, we identified the major IL-33 producers in VAT to be particular mSC subtypes, related to but distinct from adipocyte progenitor cells. We further characterize these subsets by individually isolating them and performing bulk-RNA sequencing. We explored modulation of the VAT-mSC (VmSC) landscape with physiologic variables such as age and sex, as well as pathogenic states like obesity. We uncovered a VAT Treg:stromal-cell negative regulatory loop that keeps the potent effect of IL-33 under rein. Overall design: Gene expression profiles of VmSC subtypes from young male and female mice. 2-4 mice were pooled for each biological replicate and at least 2 biological replicates were obtained per VmSC subtype.
Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors.
Specimen part, Cell line, Subject
View SamplesThis in-vitro study suggests the inflammatory environment of naive epithelial cells can induce epigenetic modulation of innate immune responses at the level of histone methylation and potentially lead to long-term impacts on anti-viral immunity.
IFN-γ Influences Epithelial Antiviral Responses via Histone Methylation of the RIG-I Promoter.
Cell line, Treatment
View SamplesSeveral studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts (CAF). However, to date a deep molecular characterization of these fibroblasts is lacking. Aim of the present study therefore was a comprehensive characterization of these fibroblasts.
Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury.
Disease
View SamplesGastrocnemius muscle biopsies were obtained from 15 health older adults without peripheral artery disease (PAD), 20 PAD patients with intermittent claudication, and 16 patients with critical limb ischemia undergoing limb amputation. Gene expression analysis was performed using RNA sequencing analysis. Overall design: Examination of gene expression differences across the clinical spectrum of PAD (healthy vs. claudicant vs. critical limb ischemia)
Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants.
Specimen part, Disease, Subject
View SamplesThe short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis. Overall design: RNA was isolated from zebrafish heart samples (3 wt and 3 miR-29-sponge) and sequenced.
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.
Specimen part, Subject
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View SamplesThe activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Specimen part
View SamplesIn response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2a (eIF2a-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2a-P cytoprotection in response to UVB. Loss of eIF2a-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2a-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2a-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5'-leader of CDKN1A mRNA. We conclude that eIF2a-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. Overall design: Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.
Translational control of a human <i>CDKN1A</i> mRNA splice variant regulates the fate of UVB-irradiated human keratinocytes.
Specimen part, Cell line, Treatment, Subject
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