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Comparison of wild type “empty” and Furin super-enhancer deleted SE EL-4 cell lines

ABSTRACT: Exceedingly abundant p300 histone acetylase binding was reported upstream Furin in mouse Th1 cells. We aimed to investigate the role of this genomic area in RNA expression by deleting it from EL-4 mouse thymoma cells and comparing the RNA expression profiles in steady-state and after PMA/ionomycin stimulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE158456 | GEO | 2021/02/18

REPOSITORIES: GEO

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Comparison of wild type “empty” and Furin super-enhancer deleted SE EL-4 cell lines

Project description:Comparison of wild type “empty” and Furin super-enhancer deleted SE EL-4 cell lines

| PRJNA665256 | ENA

Furin deficiency efect on T cells

Project description:Analysis of T-cells lacking the proprotein convertase furin. Proprotein convertases promote the proteolytic maturation of proproteins. Furin is induced in activated T-cells. Results provide insight into the function of furin in T-cells. CD4+CD62L+CD44- naive, CD4+CD62L-CD44+ memory and CD4+CD25+FoxP3+ regulatory T cells were isolated from Fur flox/flox and CD4 cre Fur flox/flox mice. Naive T cells were activated via TCR. Total RNA was extracted from all cells and hybridized to Affymetrix microarrays.

2015-08-05 | E-GEOD-67884 | biostudies-arrayexpress

Furin deficiency effect on T cells

2015-08-05 | GSE67884 | GEO

Myeloid Cell Expressed Proprotein Convertase FURIN Attenuates Inflammation

Project description:The proprotein convertase enzyme FURIN processes immature pro-proteins into functional end- products. FURIN is upregulated in activated immune cells and it regulates T-cell dependent peripheral tolerance and the Th1/Th2 balance. FURIN also promotes the infectivity of pathogens by activating bacterial toxins and by processing viral proteins. Here, we evaluated the role of FURIN in LysM+ myeloid cells in vivo. Mice with a conditional deletion of FURIN in their myeloid cells (LysMCre-fur(fl/fl)) were healthy and showed unchanged proportions of neutrophils and macrophages. Instead, LysMCre-fur(fl/fl) mice had elevated serum IL-1β levels and reduced numbers of splenocytes. An LPS injection resulted in accelerated mortality, elevated serum pro-inflammatory cytokines and upregulated numbers of pro-inflammatory macrophages. A genome-wide gene expression analysis revealed the overexpression of several pro-inflammatory genes in resting FURIN-deficient macrophages. Moreover, FURIN inhibited Nos2 and promoted the expression of Arg1, which implies that FURIN regulates the M1/M2-type macrophage balance. FURIN was required for the normal production of the bioactive TGF-β1 cytokine, but it inhibited the maturation of the inflammation-provoking TACE and Caspase-1 enzymes. In conclusion, FURIN has an anti-inflammatory function in LysM+ myeloid cells in vivo.

2016-12-30 | GSE84117 | GEO

Single-cell RNA-seq analysis of WT and Furin KO TECs

Project description:To assess the effect of Furin ablation on TEC development and heterogeneity, we detected the transcriptional profiles of 2-week-old WT and Furin KO TECs using single-cell RNA-seq. Employing an unsupervised graph-based clustering strategy, 20 clusters of TECs and 5 clusters of non-TEC contaminants were identified. After removing contaminants, 4301 WT TECs and 4086 Furin KO TECs were obtained. UMAP visualization revealed that the proportion of mTECs decreased significantly and the proportion of cTECs increased significantly in TEC-specific Furin knockout mice in comparison with WT mice. Further analysis showed that Furin ablation did not affect the proportion of mTEC I, II and III subsets, but reduced the proportion of mTEC IV subsets markedly.

2022-01-15 | GSE193456 | GEO

T cell-expressed proprotein convertase furin is essential for maintenance of peripheral tolerance

Project description:Furin is a proprotein convertase induced in activated T cells, reported to processes the anti-inflammatory cytokine TGFb-1. Herein, we show that conditional deletion of furin in T cells allowed for normal T cell development but impaired the function of regulatory T cells and effector cells, which produced less TGFb-1. Furin-deficient Treg cells, were less protective in a T cell transfer colitis model and failed to induce Foxp3 in normal T cells. Furin-deficient effector cells were inherently overly active and were resistant to suppressive activity of wild-type Tregs. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its nonredundant, essential function in regulating TGFb-1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. The current work suggests that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.

2008-06-26 | GSE11884 | GEO

Differential Gene expression of furin knockout (KO) DLD1, HCA7 and HT29 colorectal cancer cells

Project description:We created furin KO cells in three colorectal cancer cell lines (DLD1, HCA7 and HT29) using CRISPR-Cas9 genome editing. And then we performed RNA-Seq analysis in furin KO colorectal cancer cells to identify potential effect of furin on gene expression patterns in DLD1, HCA7 and HT29 cells.

2020-03-15 | GSE130969 | GEO

Loss of furin in β cells induces an mTORC1-ATF4 anabolic pathway that leads to β cell dysfunction

Project description: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. METHOD: Data obtained for the β cell specific knockout (RIP-Cre+/- furin flox/flox) and control (furin flox/flox) samples were compared to investigate the effect of furin loss on the mRNA profile of islets. Although this method does not directly provide furin targets, the notion of differential gene expression might elucidate affected cellular processes, potentially leading to upstream furin substrates.

2020-05-12 | GSE150312 | GEO

Vibrio cholerae: Wild type El Tor biotype versus crp mutant

Project description:Transcriptional profiling of an El Tor biotype crp mutant The virulent V. cholerae El Tor Ogawa strain C7258 (Peru isolate 1991) and an isogenic deletion mutant (WL7258) lacking DNA sequences encoding the cAMP receptor protein were grown in LB medium to optical density at 600 nm of 1.5. The cultures were chilled in ice, cells quickly collected by centrifugation and total RNA imediately extracted. RNAwas extracted and purified using the Trizol plus RNA purification system (Invitrogen) followed RNEasy miniElute cleanup (Qiagen). RNA samples were conserved at - 80 C and used within a week. Keywords: Genetic modification

2007-12-31 | GSE7519 | GEO

Transcription profiling of mouse naive T cells isolated from CD4+ CD62L+ CD44- T cells were isolated from Fur flox/flox and CD4 cre Fur flox/flox mice reveals T cell-expressed proprotein convertase furin is essential for maintenance of peripheral tolerance

2008-10-21 | E-GEOD-11884 | biostudies-arrayexpress

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