Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm

Frontiers in Cardiovascular Medicine

Zhifa Han¹  Huiyuan Hu²  Xiaomin Song³  Jing Wang³  Bolun Li³  Wenjun Guo³  Hongmei Zhao³  Ran Gao³  Weipeng Ge³  Yangfeng Hou³  Zhiwei Li³  Tianfei Fan³  Peiran Yang⁴ 

[1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China;First Clinical College, Xi'an Jiaotong University, ShaanXi, China;State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China;State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China;

关键词: abdominal aortic aneurysm;    single cell sequencing;    fibrocytes;    cell therapy;    cell atlas;   

DOI  :  10.3389/fcvm.2021.753711

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown