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

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...

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Autores principales:	Bolun Li, Xiaomin Song, Wenjun Guo, Yangfeng Hou, Huiyuan Hu, Weipeng Ge, Tianfei Fan, Zhifa Han, Zhiwei Li, Peiran Yang, Ran Gao, Hongmei Zhao, Jing Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	abdominal aortic aneurysm single cell sequencing fibrocytes cell therapy cell atlas Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/c4747db4c2b64de78aded45b3f1f568e
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spelling	oai:doaj.org-article:c4747db4c2b64de78aded45b3f1f568e2021-11-30T17:53:26ZSingle-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm2297-055X10.3389/fcvm.2021.753711https://doaj.org/article/c4747db4c2b64de78aded45b3f1f568e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.753711/fullhttps://doaj.org/toc/2297-055XAbdominal 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.Bolun LiXiaomin SongWenjun GuoYangfeng HouHuiyuan HuHuiyuan HuWeipeng GeTianfei FanZhifa HanZhifa HanZhiwei LiPeiran YangRan GaoHongmei ZhaoJing WangFrontiers Media S.A.articleabdominal aortic aneurysmsingle cell sequencingfibrocytescell therapycell atlasDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	abdominal aortic aneurysm single cell sequencing fibrocytes cell therapy cell atlas Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	abdominal aortic aneurysm single cell sequencing fibrocytes cell therapy cell atlas Diseases of the circulatory (Cardiovascular) system RC666-701 Bolun Li Xiaomin Song Wenjun Guo Yangfeng Hou Huiyuan Hu Huiyuan Hu Weipeng Ge Tianfei Fan Zhifa Han Zhifa Han Zhiwei Li Peiran Yang Ran Gao Hongmei Zhao Jing Wang Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
description	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.
format	article
author	Bolun Li Xiaomin Song Wenjun Guo Yangfeng Hou Huiyuan Hu Huiyuan Hu Weipeng Ge Tianfei Fan Zhifa Han Zhifa Han Zhiwei Li Peiran Yang Ran Gao Hongmei Zhao Jing Wang
author_facet	Bolun Li Xiaomin Song Wenjun Guo Yangfeng Hou Huiyuan Hu Huiyuan Hu Weipeng Ge Tianfei Fan Zhifa Han Zhifa Han Zhiwei Li Peiran Yang Ran Gao Hongmei Zhao Jing Wang
author_sort	Bolun Li
title	Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
title_short	Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
title_full	Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
title_fullStr	Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
title_full_unstemmed	Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm
title_sort	single-cell transcriptome profiles reveal fibrocytes as potential targets of cell therapies for abdominal aortic aneurysm
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c4747db4c2b64de78aded45b3f1f568e
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Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm

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