Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity

Abstract

BackgroundInflammation plays an important role in the progression of sporadic aortic dissection (AD). Immune cells, especially macrophages, infiltrate the aorta and secrete inflammatory cytokines and matrix metalloproteinases to cause degradation of the extracellular matrix, thereby contributing to the pathogenesis of AD. However, the cellular heterogeneity within these immune cells has not been fully characterized.MethodsWe used single-cell RNA sequencing to profile the transcriptomes of all immune cells in AD tissue and normal aorta. Using magnetic-activated cell sorting gating on CD45, we obtained a higher resolution identification of the immune cell subsets in the aorta.ResultsWe observed significant differences in the proportion of major immune cell subpopulations between AD and normal aorta tissues. Macrophages accounted for a higher percentage in the normal aorta, while the proportions of T cells, B cells and natural killer (NK) cells were all increased in AD tissues. Macrophage clusters that expanded in AD tissues originated primarily from circulating monocytes and expressed genes encoding proinflammatory cytokines and molecules involved in tissue repair. T and NK cells in AD tissues exhibited enhanced cytotoxic properties. A cluster of CD4+ T cells that had expanded in AD tissues was Th17-like and might contribute to the pathogenesis of AD. Cell–cell interaction analysis highlighted the increased communication between macrophages and T cells, which primarily regulated the costimulation of T cells.ConclusionsOur study provides a comprehensive characterization of immune cells in the dissected aorta with an emphasis on the role of macrophages and T cells. The information from our study improves our understanding of immune mechanisms in AD formation and helps to identify additional useful targets for early diagnosis or therapy of AD.

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection

“…Inflammation is an important factor leading to the occurrence and progression of AD [16][17][18]. A variety of immune cells can participate in the occurrence of AAD by switching to a proinflammatory phenotype and releasing inflammatory factors [18][19][20]. A previous study found that DDR-related proteins were involved in inflammatory responses [7].…”

DeCOOC Deconvoluted Hi‐C Map Characterizes the Chromatin Architecture of Cells in Physiologically Distinctive Tissues

“…More evidence came from gene expression analysis in which inflammatory factor genes, for example, S100A9, C1QA, and TIMP1, showed higher expression in visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT) (Figure 5E; Figure S15F, Supporting Information). [45][46][47] On the other hand, it is known that subcutaneous fat is more involved in energy metabolism than visceral fat. We found that energy-related metabolism GO terms (i.e., mitochondrion organization and positive regulation of angiogenesis) were significantly enriched with genes in the positive SHAP regions for M2 cells in the ULB (Figure S15B, Supporting Information).…”

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

“…development of aortic dissection (108). As for mesenchymal stem cells (MSC), because of their anti-inflammatory and repairing effects, whether they can be used in the treatment of AAD needs to be explored in more depth in the future.…”

“…Activation of Janus kinase 2 (JAK2) ( 104 , 105 ) and elevated plasma ANGPT2 levels ( 106 , 107 ) are suggestive of upregulation of pro-inflammatory cytokines in AAD. In turn, these upregulated proinflammatory cytokines lead to activation of chemotactic and other immune cells, especially neutrophils and T cells, which can further secrete inflammatory factors and granzyme, exacerbating the medial lesion and leading to the development of aortic dissection ( 108 ). As for mesenchymal stem cells (MSC), because of their anti-inflammatory and repairing effects, whether they can be used in the treatment of AAD needs to be explored in more depth in the future.…”

“…Interestingly, macrophages were found to infiltrate only at the onset of entrapment, in contrast to the long-term infiltration of macrophages and chronic degradation of the extracellular matrix that can be observed in abdominal aortic aneurysms (AAA). At the same time, depletion of circulating monocytes significantly reduced the incidence of AAD, suggesting that macrophage infiltration in the aorta is more a cause than a consequence of AAD, suggesting that macrophage infiltration is more of a “triggering” event in AAD ( 108 ). The primary molecular traits of different cell types can also be further resolved, enabling higher resolution identification between different subtypes of the same cell to reveal functional differences.…”