Potential genes and pathways along with immune cells infiltration in the progression of atherosclerosis identified via microarray gene expression dataset re-analysis
VASCULAR
Authors: Xu, Jing; Yang, Yuejin
Abstract
Objective Atherosclerosis is a chronic inflammatory process characterized by the accumulation and formation of lipid-rich plaques within the layers of the arterial wall. Although numerous studies have reported the underlying pathogenesis, no data-based studies have been conducted to analyze the potential genes and immune cells infiltration in the different stages of atherosclerosis via bioinformatics analysis. Methods In this study, we downloaded GSE100927 and GSE28829 from NCBI-GEO database. Gene ontology and pathway enrichment were performed via the DAVID database. The protein interaction network was constructed via STRING. Enriched hub genes were analyzed by the Cytoscape software. The evaluation of the infiltrating immune cells in the dataset samples was performed by the CIBERSORT algorithm. Results We identified 114 common upregulated differentially expressed genes and 22 common downregulated differentially expressed genes. (adjust p value < 0.01 and log FC >= 1). A cluster of 10 genes including CYBA, SLC11A1, FCER1G, ITGAM, ITGB2, CD53, ITGAX, VAMP8, CLEC5A, and CD300A were found to be significant. Through the deconvolution algorithm CIBERSORT, we analyzed the significant alteration of immune cells infiltration in the progression of atherosclerosis with the threshold of the Wilcoxon test at p value Conclusions These results may reveal the underlying correlations between genes and immune cells in atherosclerosis, which enable us to investigate the novel insights for the development of treatments and drugs.
A novel in vivo inducible dendritic cell ablation model in mice
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Okuyama, Megumi; Kayama, Hisako; Atarashi, Koji; Saiga, Hiroyuki; Kimura, Taishi; Waisman, Ari; Yamamoto, Masahiro; Takeda, Kiyoshi
Abstract
Dendritic cells (DCs) are involved in T cell activation via their uptake and presentation of antigens. In vivo function of DCs was analyzed using transgenic mouse models that express diphtheria toxin receptor (DTR) or the diphtheria toxin-A subunit (DTA) under the control of the CD11c/Itgax promoter. However, CD11c(+) cells are heterogeneous populations that contain several DC subsets. Thus, the in vivo function of each subset of DCs remains to be elucidated. Here, we describe a new inducible DC ablation model, in which DTR expression is induced under the CD11c/Itgax promoter after Cre-mediated excision of a stop cassette (CD11c-iDTR). Crossing of CD11c-iDTR mice with CAG-Cre transgenic mice, expressing Cre recombinase under control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter, led to the generation of mice, in which DTR was selectively expressed in CD11c(+) cells (iDTR Delta mice). We successfully deleted CD11c(+) cells in bone marrow-derived DCs in vitro and splenic CD11c(+) cells in vivo after DT treatment in iDTR Delta mice. This mouse strain will be a useful tool for generating mice lacking a specific subset of DCs using a transgenic mouse strain, in which the Cre gene is expressed by a DC subset-specific promoter. (C) 2010 Elsevier Inc. All rights reserved.