1. Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
- Author
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Bolun Li, Xiaomin Song, Wenjun Guo, Yangfeng Hou, Huiyuan Hu, Weipeng Ge, Tianfei Fan, Zhifa Han, Zhiwei Li, Peiran Yang, Ran Gao, Hongmei Zhao, and Jing Wang
- Subjects
abdominal aortic aneurysm ,single cell sequencing ,fibrocytes ,cell therapy ,cell atlas ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abdominal aortic aneurysm (AAA) is potentially life-threatening in aging population due to the risk of aortic rupture and a lack of optimal treatment. The roles of different vascular and immune cells in AAA formation and pathogenesis remain to be future characterized. Single-cell RNA sequencing was performed on an angiotensin (Ang) II-induced mouse model of AAA. Macrophages, B cells, T cells, fibroblasts, smooth muscle cells and endothelial cells were identified through bioinformatic analyses. The discovery of multiple subtypes of macrophages, such as the re-polarization of Trem2+Acp5+ osteoclast-like and M2-like macrophages toward the M1 type macrophages, indicates the heterogenous nature of macrophages during AAA development. More interestingly, we defined CD45+COL1+ fibrocytes, which was further validated by flow cytometry and immunostaining in mouse and human AAA tissues. We then reconstituted these fibrocytes into mice with Ang II-induced AAA and found the recruitment of these fibrocytes in mouse AAA. More importantly, the fibrocyte treatment exhibited a protective effect against AAA development, perhaps through modulating extracellular matrix production and thus enhancing aortic stability. Our study reveals the heterogeneity of macrophages and the involvement of a novel cell type, fibrocyte, in AAA. Fibrocyte may represent a potential cell therapy target for AAA.
- Published
- 2021
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