Single-cell sequencing combined with transcriptome analysis unravels LUM

Background: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by immune cell infiltration and vascular remodeling. B cells have been implicated in AAA pathogenesis, yet their specific roles and molecular mediators remain incompletely understood. This study aimed to investigate the immune microenvironment of AAA and elucidate the functional role of LUM in B cells using integrated multi-omics and experimental approaches. Methods: We integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptome data from GEO datasets (GSE183464, GSE226492). Key computational analyses included cell clustering, trajectory inference (CytoTRACE2, Monocle2), cell communication (CellChat), and machine learning-based feature selection (LASSO and SVM). Experimentally, primary human B cells were isolated and subjected to lentivirus-mediated LUM knockdown or overexpression, followed by Transwell co-culture with primary human aortic vascular smooth muscle cells (VSMCs). LUM expression in B cells and plasma was further validated in clinical samples, and its correlation with aneurysm diameter was analyzed. Results: Single-cell analysis identified B cells as a significantly altered immune population in AAA with enhanced communication to VSMCs. CD79A and LUM were identified as key signature genes in B cells. LUM was upregulated at both mRNA and protein levels in AAA tissues and specifically enriched in B cells. Functional experiments demonstrated that LUM expression in B cells promoted VSMC phenotypic switching toward a synthetic phenotype (upregulated OPN and downregulated contractile markers). Knockdown of LUM in B cells attenuated this effect, whereas overexpression enhanced it. Clinically, LUM protein levels in B cells and plasma increased with larger aneurysm diameter and positively correlated with maximum AAA diameter. Conclusions: This study reveals that LUM