Identification of miR-146a target genes in mouse monocyte subsets
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77159 | GEO | 2019/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Monocytes and their lineage descendants serve as a central defense system against infection and injury but if uncontrolled can also promote an excessive pathological inflammatory response. Therefore a current research goal is to understand how the organism controls the number and function of monocytes and how these variables can be tailored in therapy. Considering the evidence that monocytes are heterogeneous and exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6Chi and Ly-6Clo) and human (CD14hi and CD14lo CD16+) monocyte subsets. The single miRNA was found to significantly control the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a–mediated regulation was cell-intrinsic and depended on Relb, a member of the non-canonical NF-κB/Rel family, which is identified here as a novel miR-146a target. These observations provide novel mechanistic insights into the molecular events that regulate monocyte functional heterogeneity and identify therapeutic targets that can influence the quality and quantity of monocyte responses. 4 samples of splenic Ly-6Chi monocytes, 4 samples of splenic Ly-6Clo monocytes; both isolated from C57BL/6 mice. Each sample was generated by fluorecsence activated cell sorting from the pooled spleens of 10 mice.
2012-04-05 | E-GEOD-32370 | biostudies-arrayexpress
Project description:Monocytes and their lineage descendants serve as a central defense system against infection and injury but if uncontrolled can also promote an excessive pathological inflammatory response. Therefore a current research goal is to understand how the organism controls the number and function of monocytes and how these variables can be tailored in therapy. Considering the evidence that monocytes are heterogeneous and exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6Chi and Ly-6Clo) and human (CD14hi and CD14lo CD16+) monocyte subsets. The single miRNA was found to significantly control the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a–mediated regulation was cell-intrinsic and depended on Relb, a member of the non-canonical NF-κB/Rel family, which is identified here as a novel miR-146a target. These observations provide novel mechanistic insights into the molecular events that regulate monocyte functional heterogeneity and identify therapeutic targets that can influence the quality and quantity of monocyte responses.
2012-04-06 | GSE32370 | GEO
Project description:Murine monocytes (MC) are classified into Ly6Chigh and Ly6Clow MC. Ly6Chigh MC is the pro-inflammatory subset and the counterpart of human CD14++CD16+ intermediate MC which contributes to systemic and tissue inflammation in various metabolic disorders, including hyperhomocysteinemia (HHcy). This study aims to explore molecule signaling mediating MC subset differentiation in HHcy and control mice.Mouse white blood cell were prepared from peripheral blood and stained with antibody against CD11b, Ly6G and Ly6C and subjected for flow cytometry cell sorting. CD11b+Ly6G- cells were selected as MC. MC subsets (CD11b+Ly6G-Ly6Chigh, and CD11b+Ly6G-Ly6Clow) were sorted based on Ly6C levels. The quantification of MC was used flow cytometry analysis for Ly6Chigh and Ly6Clow MC in CT and Cbs-/-. Then, 100 ng mRNA were obtained from 100,000 sorted cells of CT and Cbs-/- (HHcy) mice. Around 30 million reads were achived and 16,487 normalized genes per sample by mRNA-Seq analysis.
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Project description:This SuperSeries is composed of the following subset Series: GSE32364: Murine blood monocyte subsets GSE32370: Regulation of monocyte functional heterogeneity by miR-146a Refer to individual Series
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Project description:In the present study, we demonstrate that NOD2 receptor triggering by muramyl dipeptide converts blood inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Muramyl dipeptide administration to Nr4a1-/- mice, which lack Ly6Clow monocytes, and to Ly6Clow-depleted mice leads to the emergence of blood patrolling monocytes expressing phenotypic profile of typical Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Furthermore using intravital microscopy in live animal models of inflammatory diseases, we observed that converted Ly6Chigh monocytes are capable of patrolling the endothelium of blood vessels and their presence contributes to reduce the inflammatory response following muramyl dipeptide injection.
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Project description:Inflammatory monocyte (MC) subset differentiation is a major feature in tissue inflammatory and atherosclerosis. The underlying molecular mechanism remains unclear. This study aims to explore molecule targets and signaling which determinate immunological features in MC subsets. ApoE-/- mice were fed a normal chow diet and switched to a high-fat (HF) diet at age 8 weeks and maintained on a HF diet for 12-14 weeks. The control C57BL/6 mice were fed a normal chow diet throughout. Blood Ly6Chigh and Ly6Clow MC subsets from control and ApoE-/- mice were isolated by flow cytometry sorting and subjected for bulk high-throughput RNA-sequencing.
2022-01-11 | GSE189097 | GEO
Project description:We have found expression of miR-146a up-regulated in gastric cancer. To identify new targets of miR-146a we profiled the transcriptome after miR-146a over-expression in the human gastric cancer cell line SNU638. SNU638 cells were transfected in triplicates with 50 nM miR-146a or control (siGlo) using Lipofectamine 2000. Total RNA was harvested 24 h after transfection using Trizol reagent. There are a total of six arrays included in this experiment, including three biological replicates of mRNA expression after miR-146a over-expression and three controls in SNU638 cells.
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Project description:TaqMan mouse miRNA array profile of LY6CHigh and LY6Clow monocyte
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Project description:MiR-146a is an important regulator of innate inflammatory responses and is also implicated in cell death and survival. Here, we identified microglia as the main cellular source of miR-146a among mouse CNS resident cells. We further characterized the phenotype of miR-146a KO microglia cells during in vivo demyelination induced by cuprizone (CPZ) and found reduced number of CD11c+ microglia in the KO compared to WT mice. Microglia were also isolated from the brain, and the proteome was analyzed by liquid chromatography mass spectrometry.
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Project description:Time-dependent profiles were recapitulated in sorted neutrophils and Ly6Chigh and Ly6Clow muscle macrophages, with a distinct pro-resolving signature observed in Ly6Clow reparative macrophages. RNA-seq analysis of macrophages stimulated with resolvin D2 (RvD2) showed similarities to transcriptional changes found during the temporal Ly6Chigh to Ly6Clow phenotypic transition. Importantly, RvD2 promoted the temporal progression from Ly6Chigh to Ly6Clow macrophages in vivo.
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