AUTHOR=Li Bolun , Song Xiaomin , Guo Wenjun , Hou Yangfeng , Hu Huiyuan , Ge Weipeng , Fan Tianfei , Han Zhifa , Li Zhiwei , Yang Peiran , Gao Ran , Zhao Hongmei , Wang Jing TITLE=Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.753711 DOI=10.3389/fcvm.2021.753711 ISSN=2297-055X 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.