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

Shiyong Wu; Shibiao Liu; Baoheng Wang; Meng Li; Chao Cheng; Hairong Zhang; Ningheng Chen; Xueli Guo

doi:10.3389/fcvm.2022.1062106

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

Front Cardiovasc Med. 2023 Jan 9:9:1062106. doi: 10.3389/fcvm.2022.1062106. eCollection 2022.

Authors

Shiyong Wu¹, Shibiao Liu¹, Baoheng Wang¹, Meng Li¹, Chao Cheng², Hairong Zhang³, Ningheng Chen¹, Xueli Guo¹

Affiliations

¹ Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² Center for Genome Analysis, Wuhan Ruixing Biotechnology Co., Ltd., Wuhan, China.
³ Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract

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.

Keywords: abdominal aortic aneurysm; in silico analysis; macrophages/monocytes; single-cell RNA sequencing; single-cell transcriptome analysis.

Grants and funding

This work was financially supported by the Joint Co-construction Project of Henan Medical Science and Technology Research Plan (No. LHGJ20200342), the Key Research & Development and Promotion of Special Project (Scientific Problem Tackling) of Henan Province (No. 202102310122), and the Medical Science and Technology Research Project (co-constructed by province and ministry) of Henan Province (No. SB201901009).