journal article·2025-12Open access

CRISPR‐MI and scRNA‐Seq Reveal TREM2's Function in Monocyte Infiltration and Macrophage Apoptosis During Abdominal Aortic Aneurysm Development

Haocheng Lu, Chao Xue, Yang Zhao, Jinjian Sun, Changzhi Zhao, Xu Zhang, Guizhen Zhao, Yaozhong Liu, Hongyu Liu, Yongjie Deng, Ying Wang, Chi Zhang, Yingjie Liu, Linjun Zeng, Ying Yang, Bolun Li, Shusi Ding, Linkang Zhou, Henry Kuang, Zanxin Wang, Wenhao Ju, Haihuan Lin, Jie Lin, Yanhong Guo, Lin Chang, Hongmei Zhao, Jing Wang, Jiandie Lin, Lemin Zheng, Y. Eugene Chen, Jifeng Zhang

Advanced Science· Volume 12· Issue 48

Abstract

Abstract Abdominal aortic aneurysm (AAA) is a life‐threatening aortic disease without effective medication. The infiltration of monocytes into the aortic wall is critical for AAA development, but the genes and pathways regulating this process remain to be elucidated. A novel method is developed for in vivo genome‐wide CRISPR/Cas9 screening of monocyte infiltration (CRISPR‐MI). By combining CRISPR‐MI with single‐cell RNA sequencing (scRNA‐Seq), this study finds that Triggering receptor expressed on myeloid cells 2 ( Trem2) is a negative regulator of monocyte infiltration into the aortic wall in early AAA induction. Trem2 knockout (KO) increases the expression of adhesion molecules, chemotactic receptors, and cytokines in monocytes. Trem2 KO promotes monocyte adhesion and migration in vitro and increases monocyte infiltration into the aortic wall in vivo. However, Trem2 KO attenuates AAA development because of prominent macrophage death at the late stage. In conclusion, CRISPR‐MI is a powerful tool for studying genes underlying monocyte infiltration in disease conditions in vivo. These findings reveal a dichotomous role of Trem2 in monocyte recruitment and macrophage survival during AAA.
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Research context

OpenAlex topics: Inflammation biomarkers and pathways · Neuroinflammation and Neurodegeneration Mechanisms · Infectious Aortic and Vascular Conditions

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pharmacology Joint Laboratory of Guangdong‐Hong Kong Universities for Vascular Homeostasis and Diseases School of Medicine Southern University of Science and Technology Shenzhen Guangdong 518033 P. R. China

Department of Internal Medicine Frankel Cardiovascular Center University of Michigan, Medical Center Ann Arbor MI 48105 USA

Department of Internal Medicine Rochester General Hospital Rochester NY 14621 USA

Department of General &Vascular Surgery Xiangya Hospital Central South University Changsha Hunan 410008 P. R. China

Yazhouwan National Laboratory Sanya 572024 P. R. China

Laboratory of Translational Genetics Division of Cancer Epidemiology & Genetics National Cancer Institute Bethesda MD 20892 USA

Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection Capital Medical University Beijing 100050 China

Life Sciences Institute University of Michigan Ann Arbor MI 48109 USA

Department of Cardiovascular Surgery The University of Hong Kong‐Shenzhen Hospital Guangdong 518031 P. R. China

Department of Structural Heart Disease National Center for Cardiovascular Disease China & Fuwai Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100037 P. R. China

National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences Beijing 100037 P. R. China

Cardiology Department The First Affiliated Hospital of Wenzhou Medical University 325000 Wenzhou P. R. China

State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100050 P. R. China

Department of Cell and Developmental Biology University of Michigan Medical Center Ann Arbor MI 48109 USA

The Institute of Cardiovascular Sciences School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science of Ministry of Education NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Health Science Center Peking University Beijing 100191 P. R. China

Funding

National Natural Science Foundation of China · National Institutes of Health · Natural Science Foundation of Hunan Province

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