Deciphering Cell-Cell Communication in Abdominal Aortic Aneurysm From Single-Cell RNA Transcriptomic Data

Abstract

Cell-cell communication coordinates cellular differentiation, tissue homeostasis, and immune responses in states of health and disease. In abdominal aortic aneurysm (AAA), a relatively common and potentially life-threatening vascular disease, intercellular communications between multiple cell types are not fully understood. In this study, we analyzed published single-cell RNA sequencing (scRNA-seq) datasets generated from the murine CaCl2 model, perivascular elastase model, Angiotensin II model, and human AAA using bioinformatic approaches. We inferred the intercellular communication network in each experimental AAA model and human AAA and predicted commonly altered signaling pathways, paying particular attention to thrombospondin (THBS) signaling between different cell populations. Together, our analysis inferred intercellular signaling in AAA based on single-cell transcriptomics. This work provides important insight into cell-cell communications in AAA and has laid the groundwork for future experimental investigations that can elucidate the cell signaling pathways driving AAA.

Single-cell transcriptome in silico analysis reveals conserved regulatory programs in macrophages/monocytes of abdominal aortic aneurysm from multiple mouse models and human

“…To further analyze the scRNA-seq datasets of Mφ/Mo from both mouse and human, it’s found that two genes, IL-1B and THBS1 , were co-upregulated and no gene was co-downregulated in the four datasets. This fully demonstrated the critical role of IL-1B and THBS1 in AAA, which is consistent with the previous discussion and related literature ( 36 , 39 ). The formation mechanisms of AAA induced by elastase, CaCl 2 as well as Ang II were different, and none of them can completely replace human AAA process.…”

“…THBSs overexpression may affect the formation of matrix cells and inhibit the activity of matrix proteins, thus destroying the structure of extracellular matrix and affecting the AAA occurrence ( 38 ). Yang predicted commonly altered signaling pathways by using intercellular communication networks in different experimental AAA models and human AAA, with a particular focus on THBS signaling among different cell populations ( 39 ). These results suggested that these genes were vital in the occurrence and development of AAA and worth further exploring.…”

A vein wall cell atlas of murine venous thrombosis determined by single-cell RNA sequencing

“…Cell-cell communication. We sought to predict how different cell populations within the vein wall may communicate with one another using CellChat, an R toolkit that contains a database of 2,021 validated murine molecular interactions between signaling ligands, receptors, and their cofactors 22,23 .…”

Identification of cellular heterogeneity and key signaling pathways associated with vascular remodeling and calcification in young and old primate aortas based on single-cell analysis

“…Moreover, THBS are evolutionarily conserved, calcium-binding glycoproteins that contribute to wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis [28]. Recent analysis found that THBS signaling pathway was associated with abdominal aortic aneurysm [22], which is a kind of aged related cardiovascular disease. These results indicated that the cellular communications of SMCs have changed during aging.…”

“…CellChat is an analytic tool that can be used to analyze intercellular communication networks from scRNA-seq data [21]. It has been successfully employed to investigate the intercellular communication status of healthy and diseased aortas [22]. Here, we used CellChat to deduce the cellular communication of age vasculature with published datasets.…”