An intersegmental single-cell profile reveals aortic heterogeneity and identifies a novel Malat1+ vascular smooth muscle subtype involved in abdominal aortic aneurysm formation

Yu, Liwen; Zhang, Jie; Gao, Amy; Wang, Zunzhe; Yu, Fangpu; Guo, Xiping; Su, Guohai; Zhang, Yun; Zhang, Meng; Zhang, Cheng

doi:10.1038/s41392-022-00943-x

Cited by 24 publications

(21 citation statements)

References 41 publications

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“…Although the single-cell map of SMCs and macrophages in aortic aneurysm has been reported ( Zilionis et al, 2019 ; Davis et al, 2021 ; Liu et al, 2022 ; Yu et al, 2022 ), we reveal an innovative conservation of gene expression profiles between mice and humans. First, we see coherence of SMC subpopulations.…”

Section: Discussionmentioning

confidence: 59%

Comparative analysis of thoracic and abdominal aortic aneurysms across the segment and species at the single-cell level

Xie²,

Cheng³

et al. 2023

Front. Pharmacol.

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Introduction: Aortic aneurysm is a life-threatening disease resulted from progressive dilatation of the aorta, which can be subdivided into thoracic and abdominal aortic aneurysms. Sustained subcutaneous angiotensin II infusion can induce aortic aneurysms in mice. However, the relevance of using angiotensin II induction model to study aneurysm disease and the degree of commonality between species remain elusive.Methods: We utilized scRNA-seq to infer aortic cell sub-structures and transcriptional profiles in clinical patient TAAs and AAAs, as well as mouse models of corresponding diseases (Ang II induction) and in healthy mouse aorta. Unbiased comparison between mice and humans explored the possible reasonability and utility of mouse Ang II-induced aortic aneurysm as a model for human aortic aneurysm diseases. Meanwhile, we performed comparative analysis of aortic aneurysms between TAA and AAA in both organisms.Results and Discussion: We demonstrated similarities and differences of changes in the components of human and mouse cell types, and our unbiased comparison between mouse and human identified well conserved subpopulations of SMCs and macrophages. Furthermore, the results of our comparative analyses suggested different biological functions and distinct potential pathogenic genes for thoracic and abdominal aortic aneurysms. MIF and SPP1 signaling networks participated in aortic aneurysm in both organisms. This study maps aortic aneurysm and offers opportunities for future researches to investigate the potential of subpopulations or marker genes as therapy targets.

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Section: Discussionmentioning

confidence: 59%

Comparative analysis of thoracic and abdominal aortic aneurysms across the segment and species at the single-cell level

Xie²,

Cheng³

et al. 2023

Front. Pharmacol.

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“…Single-cell RNA sequencing is a contemporary and powerful technique for determining transcriptome gene profiles at the cellular level. ScRNA-seq has been recently used by many researchers to study the transcriptome profiles of aortic aneurysm tissues in humans and experimental animals at single-cell resolution (14,(20)(21)(22)33). A comprehensive and unbiased genetic analysis by scRNA-seq can lead to a better understanding of cell-specific molecular signatures of AAA under physiological and pathophysiological conditions (34).…”

Section: Discussionmentioning

confidence: 99%

“…Unique Molecular Identifier (UMI) count matrix for AAA and control sample scRNA-seq data of 4 datasets (14,(20)(21)(22) were downloaded from the GEO database. The UMI count matrix was converted from R package Seurat to Seurat objects (23) (version 4.0.4).…”

Section: Retrieval and Process Of Public Datamentioning

confidence: 99%

“…Yang induced AAA in C57BL/6J mouse by perivascular application of CaCl 2 for scRNA-seq, and analyzed the transcriptional profile and potential functional characteristics of populations in VSMCs, fibroblasts and macrophages ( 20 ). Yu demonstrated the key role of Malat1 VSMCs in the occurrence and progression of AAA by scRNA-seq of Ang II-induced AAA treated with or without the inhibitor ( 21 ). Zhao demonstrated the heterogeneity and cellular response of VSMCs and Mφ/Mo in the progression of AAA by scRNA-seq of elastase-induced AAA ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

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

Liu²,

Wang³

et al. 2023

Front. Cardiovasc. Med.

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Abdominal aortic aneurysm (AAA) is a life-threatening disease and there is currently a lack of effective treatment to prevent it rupturing. ScRNA-seq studies of AAA are still lacking. In the study, we analyzed the published AAA scRNA-seq datasets from the mouse elastase-induced model, CaCl2 treatment model, Ang II-induced model and human by using bioinformatic approaches and in silico analysis. A total of 26 cell clusters were obtained and 11 cell types were identified from multiple mouse AAA models. Also, the proportion of Mφ/Mo increased in the AAA group and Mφ/Mo was divided into seven subtypes. There were significant differences in transcriptional regulation patterns of Mφ/Mo in different AAA models. The enrichment pathways of upregulated or downregulated genes from Mφ/Mo in the three mouse datasets were different. The actived regulons of Mφ/Mo had strong specificity and the repressed regulons showed high consistency. The co-upregulated genes as well as actived regulons and co-downregulated genes as well as repressed regulons were closely correlated and formed regulatory networks. Mφ/Mo from human AAA dataset was divided into five subtypes. The proportion of three macrophage subpopulations increased but the proportion of two monocyte subpopulations decreased. In the AAA group, the upregulated or downregulated genes of Mφ/Mo were enriched in different pathways. After further analyzing the genes in Mφ/Mo of both mouse and human scRNA-seq datasets, two genes were upregulated in the four datasets, IL-1B and THBS1. In conclusion, in silico analysis of scRNA-seq revealed that Mφ/Mo and their regulatory related genes as well as interaction networks played an important role in the pathogenesis of AAA.

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“…Recent research have employed scRNA-seq to identify the cell types present within AAA walls and to understand their functions in the disease's genesis and progression. One study, for example, used scRNAseq to identify a population of highly active smooth muscle cells (SMCs) in AAA and discovered that these cells expressed genes related to in ammation and extracellular matrix remodeling (Yu et al, 2022;Zhao et al, 2021). Another study employed scRNA-seq to identify a larger population of macrophages in greater numbers in AAA than the healthy aorta and discovered that these cells expressed immune response and tissue repair genes.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing applications in abdominal aortic aneurysm: A mini review

Algabri

2023

Preprint

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In the past decade, advances in single-cell RNA sequencing (scRNA-seq) technology have revolutionized biomedical research, enabling the characterization and analysis of the transcriptomes of single cells with remarkable precision and throughput. Specifically, scRNA-seq has assisted in the identification of novel or rare cell types, the analysis of single-cell trajectory formation and stem or progenitor cell development, and the single-cell resolution comparison of healthy and disease-related tissues. The generation of cell atlases of the mammalian heart and blood vessels, as well as the elucidation of mechanisms involved in cardiovascular development and stem or progenitor cell differentiation, demonstrate the importance of these applications to the advancement of cardiovascular research over the past decade. This review examines the applications of scRNAseq in AAA research and discusses the molecular pathways of cardiovascular development and diseases uncovered by scRNA-seq analysis that could be implemented in clinical practice.

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An intersegmental single-cell profile reveals aortic heterogeneity and identifies a novel Malat1+ vascular smooth muscle subtype involved in abdominal aortic aneurysm formation

Cited by 24 publications

References 41 publications

Comparative analysis of thoracic and abdominal aortic aneurysms across the segment and species at the single-cell level

Comparative analysis of thoracic and abdominal aortic aneurysms across the segment and species at the single-cell level

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

Single-cell RNA sequencing applications in abdominal aortic aneurysm: A mini review

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