Cross-species single-cell transcriptomic analysis unveils conserved myeloid signatures in abdominal aortic aneurysm: implications for therapeutic targeting

Background: Abdominal aortic aneurysm (AAA), a serious vascular disease, is fundamentally linked to adaptive and innate immune responses. Myeloid cells (such as various macrophages and monocytes) play a crucial role in inflammatory responses and vascular injury or repair. Materials and Methods: Using single-cell sequencing, we analyzed over 130 000 cells from human AAA samples and mouse models, performing functional and genetic classification of myeloid macrophages. For genes with high cross-species expression, we construct cell-based in vitro models to further explore their roles in inflammation. Results: We identified eight conserved macrophage subsets shared between humans and mice, underscoring the robustness of mouse models in mimicking human disease mechanisms and revealing potential for AAA translational research. Advanced tools like Monocle 3 and CellChat helped us explore immunoregulatory functions, track developmental trajectories, and map cell communication networks, discovering high cross-species expression of Secreted Phosphoprotein 1 (SPP1)/CD44. In vitro model experiments showed that SPP1 was positively correlated with M1 polarization of macrophages and negatively correlated with M2 polarization. Additionally, SCENIC identified common transcriptional regulators in the AAA environment, validating potential regulatory transcription factor targets. Conclusion: This study highlights the critical role of myeloid cells in AAA pathogenesis, confirms the potential of mouse models for therapeutic interventions, and uncovers significant crosstalk between transcription factors, deepening the understanding of AAA pathology and identifying potential therapeutic targets.