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Total RNA sequencing data of murine bone marrow derived macrophages from Apoe-/- and Apoe-/-/Treml4-/- mice stimulated with oxLDL

ABSTRACT: Treml4 has been recently caracterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determined if Treml4 expression correlates with lipid laden macrophages and, second, investigate how gene expression is affected by Treml4 expression status utlizing a global knockdown mouse for Treml4 under the apolipoprotein deficient background.

ORGANISM(S): Mus musculus

PROVIDER: GSE145380 | GEO | 2020/03/01

REPOSITORIES: GEO

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RNA-seq of human PBMC's and blood derived macrophages from healthy donors carrying the common (non permissive Treml4 expression) or minor (permissive Treml4 expression) allele for rs2803496 which controls Treml4 expression

Project description:Treml4 has been recently characterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determine if Treml4 expression correlates to inflammatory activation and, second, investigate how inflammatory gene expression is affected by Treml4 expression status in donors carrying the minor allele for a rs2803496.

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Project description:Treml4 has been recently characterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determined if Treml4 expression correlates to inflammatory activation and, second, investigate how inflammatory gene expression is affected by Treml4 expression status utlizing a global knockdown mouse for Treml4.

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Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

Project description:Peripheral blood RNA-Seq from human coronary artery calcification cases and controls; Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. Eight cases and eight controls (matched for gender, age and ancestry); RNA sequencing of peripheral blood from a discovery set of eight CAC cases and eight matched controls was used to identify dysregulated genes, which were validated using the NanoString® and Affymetrix GeneChip® Human Exon ST Array platforms. The median CAC scores for cases in the screening and validation sets were 1531.5 and 668.5, respectively, while all controls had a score of zero.

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Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

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Total RNA sequencing data of murine bone marrow derived macrophages from Apoe-/- and Apoe-/-/Treml4-/- mice stimulated with oxLDL

Project description:Total RNA sequencing data of murine bone marrow derived macrophages from Apoe-/- and Apoe-/-/Treml4-/- mice stimulated with oxLDL

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Project description:RNA-seq of human PBMC's and blood derived macrophages from healthy donors carrying the common (non permissive Treml4 expression) or minor (permissive Treml4 expression) allele for rs2803496 which controls Treml4 expression

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Transcriptional analysis of TREM-1+ and TREM-1- airway eosinophils during allergic inflammation

Project description:Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) an innate receptor that canonically amplifies inflammatory signaling in neutrophils and monocytes, plays a central role in regulating lung inflammation. Utilizing a murine model of asthma, flow cytometry revealed TREM-1+ eosinophils in the lung tissue and airway during allergic airway inflammation. TREM-1 expression was restricted to recruited, inflammatory eosinophils. Expression was induced on bone marrow derived eosinophils by incubation with IL-33, LPS, or GM-CSF. Compared to TREM-1- airway eosinophils, TREM-1+ eosinophils were enriched for pro-inflammatory gene sets including migration, respiratory burst, and cytokine production. Unexpectedly, eosinophil-specific ablation of TREM-1 increased airway IL-5 and lung tissue eosinophil accumulation. Further investigation of transcriptional data revealed apoptosis related gene sets were enriched in TREM-1+ eosinophils. Annexin V staining demonstrated higher rates of apoptosis among TREM-1+ eosinophils compared to TREM-1- eosinophils in the inflammatory airway. In vitro, Trem1/3-/- eosinophils were protected from apoptosis. Finally, inhibition of reactive oxygen species production with diphenyleneiodonium protected WT bone marrow derived eosinophils from apoptosis more than Trem1/3-/- eosinophils, suggesting that superoxide accounted for more apoptosis in WT cells. These data demonstrate protein level expression of TREM-1 by eosinophils for the first time, define a population of TREM-1+ inflammatory eosinophils, and reveal that eosinophil TREM-1 restricts key features of type 2 lung inflammation.

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