Project description:We report the single cell transcriptome of CD4+ T cells from atherosclerotic aortas from ApoE-deficient mice that have been fed a western diet (WD) with aggravated atherosclerosis or with a standard chow diet (CD) with moderate atherosclerosis. We show that aortic T cells have a unique transcriptome with a mixed phenotype overlapping with T-regulatory and pathogenic T-helper type -1 and -17 cells.
Project description:The aim of this study was to analyze the transcriptome of diverse Nrf2-deficient macrophage subpopulations from murine atherosclerotic aortas. Mice with transcriptionally inactive Nrf2 in Cdh5-expressing cells (Nrf2Cdh5tKO) were used in the experiments. These mice lack transcriptional Nrf2 activity in endothelial cells, but also in a proportion of leukocytes. We confirmed that the bone marrow-derived and tissue-resident macrophages isolated from Nrf2Cdh5tKO mice exhibit a significant decline in Nrf2 activity. Atherosclerosis was induced in Nrf2Cdh5tKO and appropriate control mice via adeno-associated viral vector (AAV)-mediated overexpression of murine proprotein convertase subtilisin/kexin type 9 (Pcsk9) in the liver and high-fat diet feeding. After 21 weeks, live aortic cells were sorted on FACS and single-cell RNA sequencing (scRNA-seq) was performed. Our findings indicate that Nrf2 deficiency in aortic macrophages leads to subtype-specific transcriptomic changes associated with inflammation, iron homeostasis, cell injury or death pathways. This may help understanding the role of aging-associated decline of Nrf2 activity and the function of specific macrophage subtypes in atherosclerotic lesion development.
Project description:We have applied 10X single-cell RNA sequencing (scRNA-seq) technique to examine the cell type specific transcriptomes of heterogeneous cell populations in atherosclerotic aortas isolated from Oasl1+/+Apoe-/- and Oasl1-/-Apoe-/- mice.
Project description:Atherosclerosis leads to vascular lesions that involve major rearrangements of the vascular proteome, especially of the extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation of plaques by single-run, high-resolution mass spectrometry (MS)-based proteomics. To probe localization on a proteome-wide scale, we employed quantitative detergent solubility profiling. This compartment- and time-resolved resource of atherogenesis comprised 5,117 proteins, 182 of which changed their expression status in response to vessel maturation and atherosclerotic plaque development. In the insoluble ECM proteome, 65 proteins significantly changed, including relevant collagens, matrix metalloproteinases and macrophage specific proteins.
Project description:To better understand the role of lineage in smooth muscle cell heterogenity along the length of the aorta, we performed bulk RNA-sequencing transcriptomic analysis on secondary heart field (SHF)-derived and cardiac neural crest derived (CNC)-derived sorted cells from murine aortas.
Project description:We report the single cell transcriptome of atherosclerosis-specific murine CD4+ T cells that recognize a peptide from ApoB-100, the core protein of low-density lipoprotein (LDL). Our data reveal a unique single cell transcriptome of ApoB-specific T cells that is similar to T-regulatory T but shows an overlap with the transcriptome of pathogenic T-helper type -1 and -17 cells on a single cell level.