STOmics technology:BGI Stereomics Stereo-Seq

Data type:Spatial transcriptomics

Sample scope:Multiisolate

Summary:Atherosclerosis is a chronic process that leads to the buildup of plaque inside arterial walls and is a key factor underlying cardiovascular disease-related mortality. However, the mechanisms involved in its formation remain largely unclear. The aorta's thin, strip-like topology, combined with its complex environment and remarkable plasticity -- with the capacity for transdifferentiation between multiple cell types under physiological and pathophysiological conditions -- has hindered molecular discoveries in vascular single-cell biology. Fortunately, this intricate spatiotemporal heterogeneity, always concurrent with cell migration across the aortic layers during plaque formation, could potentially be captured through spatial transcriptomics (ST). Using ST technology at cellular resolution, we present a spatial atlas of a murine model of atherosclerosis, comprising over one million cells across multiple stages of atherogenesis. We computationally digitize the aortic stratification to record cell migration and transdifferentiation in situ, constructing molecular trajectories to account for the progression of atherosclerosis. Our systematic study explores the intricate interactions between smooth muscle cell modulation and endothelial-to-mesenchymal transition, identifying novel transcription factors involved in this process, which we validated experimentally. Based on these findings, we further verified that secreted plasma midkine (MDK) could serve as a potential biomarker for early clinical detection and therapeutic target for atherosclerosis. Taken together, we demonstrate an experimental and computational framework for the spatiotemporal investigation of atherosclerosis, fostering more comprehensive research and clinical insights.

Contributor(s):Yinqi Bai, Yujia Liu, Jiajun Yao, Yan Li, Jinpei Lin et al.

Submitter:方琦(Qi Fang),BGI

Release date:2025-12-31

Updated:2025-12-31