Dataset Information

Single-cell RNA sequencing of aortic cellular in ApoE-/- mice and MSC_ITGB3-treated ApoE-/- mice

ABSTRACT: We reports 33,782 individual cells from HFD-fed mouse aortas with or without MSC_ITGB3 treatment were subjected to single-cell RNA sequencing. We generated a compendium of 30 cell clusters, mainly smooth muscle cells (SMCs), endothelial cells (ECs), and immune cells. In the HFD group, genes associated with proliferation, migration, and collagen were highly expressed in the major SMC subpopulations. However, the expression of contraction-related genes in SMC subpopulations was significantly higher in the MSC_ITGB3 group than in the HFD group. After HFD consumption, EC subpopulations with active PI3K-Akt signaling pathways, extracellular matrix-receptor interaction, and contraction-related genes were significantly enriched. In the MSC_ITGB3 group, the number of dendritic cells positively correlated with atherosclerotic lesion progression and contributed to lipid accumulation, and inflammatory factor levels decreased. These data on the composition, signaling pathways, and cellular communication of the aorta cells following stem cell treatment and atherosclerotic disease progression may help improve atherosclerosis treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE238011 | GEO | 2026/07/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Cardiovascular disease is the leading cause of death in developed countries and there is compelling evidence that the majority of these fatalities are secondary to rupture of unstable atherosclerotic plaques. However, the mechanisms that control plaque stability are poorly understood, although it is widely believed that plaques having a decreased ratio of cells positive for smooth muscle cell (SMC) markers such as ACTA2 relative to macrophage markers are more likely to rupture. Herein we employMyh11-CreERT2 ROSA floxed STOP eYFP Apoe-/- mice to trace SMC lineage and show that traditional methods for detecting SMCs based on immunostaining for SMC markers like ACTA2 are unable to detect 82% of SMC-derived cells within advanced atherosclerotic lesions. Moreover, we show that these SMC-derived cells within advanced lesions exhibit multiple phenotypes including activation of multiple markers of macrophages, mesenchymal stem cells (MSC), and myofibroblasts (MF). Importantly, we show that SMC-derived macrophage like cells are phagocytic based on electron microscope YFP immunolabeling. In addition, results of single cell epigenetic assays developed in our lab shows that nearly 20% of macrophage-like cells within human lesions are of SMC not myeloid origin. These phenotypic transitions appear to be critical in lesion pathogenesis, in that we show that SMC-specific conditional knockout (KO) of the pluripotency factor, Krüppel-like factor 4 (KLF4), resulted in marked reductions in lesion size, increases in multiple indices of plaque stability, and reduced numbers of SMC-derived MSC- and macrophage-like cells. Finally, we show that cholesterol loading of cultured SMC is associated with activation of multiple markers of macrophages and MSC, secretion of pro-inflammatory cytokines, and increased phagocytosis, all of which are Klf4 dependent. Taken together, results indicate that the contribution of SMCs within atherosclerotic plaques has been greatly underestimated, and that loss of Klf4 within SMC result in major changes in SMC phenotype and function that play a major role in lesion pathogenesis. Examination of KLF4 transcription factor in an atherosclerosis setting

Dataset Information

Single-cell RNA sequencing of aortic cellular in ApoE-/- mice and MSC_ITGB3-treated ApoE-/- mice

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets