Single cell RNA sequencing of aortic CD45+ cells and foam cells from atherosclerotic aorta
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116240 | GEO | 2018/08/30
REPOSITORIES: GEO
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Project description:Macrophages in atherosclerotic aorta are major population in lesion and contributes to lesion formation by becoming foam cells. To investigate in determine diversity of arterial macrophage, we extracted aorta intima resident macrophages (CD11c+ MHC II+ CD64+ macrophages from C57BL/6 mice, as well as adventitia macrophages from atherosclerotic aorta (which complement our prior submissions of foamy and non-foamy intima macrophage). Our data identify unique gene expression signatures for these different macrophage populations in the aorta.
2020-07-23 | GSE154921 | GEO
Project description:Macrophages in atherosclerotic aorta are major population in lesion and contributes to lesion formation by becoming foam cells. To investigate in vivo transcriptome profiles of those macrophages, we extracted foamy and non-foamy macrophages from atherosclerotic aorta using lipid probe-based flow cytometry sorting. Our data indicates that intima non-foamy and foamy macrophages show different mRNA expressions. Rather than non-foamy macrophages, foamy macrophages expressed more genes related to cholesterol metabolism, oxidative phosphorylation, lysosome and so on. The non-foamy macrophages expressed more genes related to immune response (Il-1b related pathways, TNF, TLR signaling pathways) than foamy macrophages.
2018-08-30 | GSE116239 | GEO
Project description:Single cell RNA sequencing of aortic CD45+ cells and foam cells from atherosclerotic aorta
| PRJNA477843 | ENA
Project description:Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-? action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-? family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells. Samples (n=4/group): Foam cell macrophages (FCM) isolated from inflammatory sponges placed in ApoE null mice fed a high-fat diet (n=4), non-foamy macrophages (NFM) isolated from inflammatory sponges placed in control mice fed a normal diet (n=4).
2015-07-23 | E-GEOD-70126 | biostudies-arrayexpress
Project description:C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr–/– mice. We discovered that C.pn-induced extracellular IL-1β triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3–/– mice in both hyperlipidemic and C.pn infection models. We sued microarrays to detail the gene expression underlying C.pn and ox-LDL treatment on mice periteneal macrophages to study the regulating of ABCA1 related genes with NLRP3 manutation
2018-05-18 | GSE114565 | GEO
Project description:Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, the differentially expressed proteins were identified. Methods: In this paper, human monocytes, macrophage colony-stimulating factor induced macrophages, and oxidized low-density lipoprotein induced foam cells were cultured, and tandem mass tag (TMT) labeling combined with mass spectrometry (MS) were performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively, using a cutoff of 1.5-fold change. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus and upregulated DEPs of foam cells/macrophages mostly located in the plasma membrane and extracellular. Functional analysis of DEPs demonstrated that cholesterol metabolism related proteins were upregulated in foam cells, whereas the immune response-related proteins were downregulated in foam cells. The protein-interaction network showed that the DEPs with the highest interaction intensity between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: This study for the first time to perform quantitative proteomic investigation by TMT labeling and LC-MS/MS to identify differentially expressed proteins in human monocyte, macrophage, and foam cell. The results confirmed cholesterol metabolism was upregulated in foam cells, while immune response was suppressed, which suggested that foam cells were not the population that promote inflammation. In addition, KEGG enrichment analysis and protein-protein interaction indicated that the differentially expressed proteins locating in the endoplasmic reticulum and lysosomes may be key targets to regulate foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism involved in the transformation of macrophages to foam cells.
2022-02-15 | PXD028363 | Pride
Project description:Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-β action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-β family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells.
2015-07-23 | GSE70126 | GEO
Project description:Atherosclerosis is modulated by immune cells. Understanding the diversity and heterogeneity in the aorta in steady state, as well as during different stages of disease will help to determine mechanisms promoting disease progression. To characterize the immune cells, we performed single cell RNA sequencing of aortic CD45+ leukocytes from C57BL/6 (WT) on chow diet and early disease Ldlr-/- mice fed high fat diet (HFD) for 21-days. The single cell RNA-seq analyses revealed the heterogeneity of aortic macrophages in steady state and early atherosclerotic disease.
2020-07-22 | GSE154817 | GEO
Project description:In atherosclerosis progression and regression, monocytes or monocyte-derived macrophages are the major immune cells in the plaque. It is important to understand the fate and characteristics of monocyte/macrophage during the plaque progression and regression. To characterize the fate of monocytes/macrophages, we performed single cell RNA sequencing of fate-mapped aortic CX3CR1-derived monocytes/macrophages from Cx3cr1CreERT2-IRES-YFP/+Rosa26floxed-tdTomato/+ mice with AAV-PCSK9 injection and fed a Western Diet. The single cell RNA-seq analyses revealed the heterogeneity of aortic macrophages and identified a stem-like cell cluster in atherosclerotic aorta.
2019-02-21 | GSE123587 | GEO
Project description:Atherosclerosis is a systemic and chronic inflammatory disease propagated by monocytes and macrophages. Yet, our knowledge on how transcriptional profiles of these cells evolve in time and space is limited. We aimed at characterizing gene expression changes in site-specific macrophages, i.e. atherosclerotic aorta versus remote peritoneal cavity, and in circulating monocytes during the course of atherosclerosis initiation and progression in Apoe deficient mice. Constructing a comparative directory of cell type- and disease stage-specific whole transcriptome information, we identified a distinctive gene regulation profile of aortic macrophages. Overall 1149 differentially expressed genes (DEG) were involved in the biological modulation of aortic macrophages, and they were further categorized into regulated early, late, and transitorily throughout the disease course. The commonality of gene regulation was surprisingly low among the three investigated cell types. Through complementary interrogation of murine and human single cell RNA sequencing datasets, we showcased the practicality of our directory, using the selected gene, Glycoprotein Nmb (Gpnmb), whose expression in aortic macrophages, and a subset of foamy macrophages in particular, strongly correlated with disease advancement during atherosclerosis initiation and progression. Our study provides a unique toolset to explore gene regulation of macrophage-related biological processes in and outside the atheromatous plaque at early and advanced disease stages for pathomechanistic insight and therapeutic target screening.
2023-04-06 | GSE213189 | GEO