CRISPR-MI and scRNA-Seq Reveal TREM2's Function in Monocyte Infiltration and Macrophage Apoptosis During Abdominal Aortic Aneurysm Development
Department
Internal Medicine
Document Type
Article
Publication Title
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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.
First Page
e12227
DOI
10.1002/advs.202412227
Volume
12
Issue
48
Publication Date
12-1-2025
Medical Subject Headings
Aortic Aneurysm, Abdominal; Monocytes; Animals; Receptors, Immunologic; Macrophages; Membrane Glycoproteins; Mice; CRISPR-Cas Systems; Apoptosis; Mice, Knockout; Male; Mice, Inbred C57BL; Humans; Disease Models, Animal; RNA-Seq; Clustered Regularly Interspaced Short Palindromic Repeats; Single-Cell Gene Expression Analysis
PubMed ID
41058009
Recommended Citation
Lu, H., Xue, C., Zhao, Y., Sun, J., Zhao, C., Zhang, X., Zhao, G., Liu, Y., Liu, H., Deng, Y., Wang, Y., Zhang, C., Liu, Y., Zeng, L., Yang, Y., Li, B., Ding, S., Zhou, L., Kuang, H., Wang, Z., Ju, W., Lin, H., Lin, J., Guo, Y., Chang, L., Zhao, H., Wang, J., Lin, J., Zheng, L., Chen, Y., & Zhang, J. (2025). CRISPR-MI and scRNA-Seq Reveal TREM2's Function in Monocyte Infiltration and Macrophage Apoptosis During Abdominal Aortic Aneurysm Development. Advanced Science (Weinheim, Baden-Wurttemberg, Germany), 12 (48), e12227. https://doi.org/10.1002/advs.202412227