CRISPR‐MI and scRNA‐Seq Reveal TREM2's Function in Monocyte Infiltration and Macrophage Apoptosis During Abdominal Aortic Aneurysm Development
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.
Authors
- Linjun Zeng (ORCID: https://orcid.org/0000-0001-6791-2109)
- Hongmei Zhao (ORCID: https://orcid.org/0000-0002-2701-159X)
- Changzhi Zhao
- Y. Eugene Chen
- Bolun Li (ORCID: https://orcid.org/0000-0002-7078-7107)
- Guizhen Zhao (ORCID: https://orcid.org/0000-0002-2648-8986)
- Shusi Ding (ORCID: https://orcid.org/0000-0002-0360-9896)
- Yaozhong Liu (ORCID: https://orcid.org/0000-0003-1994-2025)
- Wenhao Ju
- Haihuan Lin (ORCID: https://orcid.org/0000-0001-5836-8316)
- Linkang Zhou (ORCID: https://orcid.org/0000-0002-7009-5776)
- Yongjie Deng
- Hong Yu Liu (ORCID: https://orcid.org/0000-0003-1754-0145)
- Zanxin Wang (ORCID: https://orcid.org/0009-0009-5817-3741)
- Haocheng Lu (ORCID: https://orcid.org/0000-0002-5740-8010)
- Jiandie D. Lin (ORCID: https://orcid.org/0000-0001-8069-5647)
- Lin Chang (ORCID: https://orcid.org/0000-0002-5621-8426)
- Xu Zhang (ORCID: https://orcid.org/0000-0003-3492-4618)
- Yanhong Guo (ORCID: https://orcid.org/0000-0002-3334-9159)
- Ying Wang (ORCID: https://orcid.org/0000-0002-9659-977X)
- Henry Kuang (ORCID: https://orcid.org/0000-0002-1957-6726)
- Yang Zhao (ORCID: https://orcid.org/0000-0002-1428-5145)
- Yingjie Liu (ORCID: https://orcid.org/0000-0003-0073-1842)
- Jie Lin
- Chi Zhang (ORCID: https://orcid.org/0000-0001-7698-6601)
- Jing Wang (ORCID: https://orcid.org/0000-0003-2891-670X)
- Jifeng Zhang (ORCID: https://orcid.org/0000-0001-5161-4705)
- Chao Xue (ORCID: https://orcid.org/0000-0002-6528-3975)
- Ying Yang (ORCID: https://orcid.org/0000-0003-2457-5792)
- Lemin Zheng (ORCID: https://orcid.org/0000-0003-4473-6936)
- Jinjian Sun
Institutions
- Central South University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Huazhong Agricultural University (CN)
- Wenzhou Medical University (CN)
- University of Michigan (US)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Southern University of Science and Technology (CN)
- Beijing Tian Tan Hospital (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Ministry of Education (RO)
- Rochester General Hospital (US)
- Michigan Medicine (US)
- Ann Arbor VA Medical Center (US)
- National Cancer Institute (US)
- University of Hong Kong - Shenzhen Hospital (CN)
- Cancer Genetics (United States) (US)
- Xiangya Hospital Central South University (CN)
- Fu Wai Hospital (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-10-07
- DOI
- https://doi.org/10.1002/advs.202412227
- Citations
- 1
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.80