Unveiling Molecular Diversity in Cerebral Thrombi via Spatial Transcriptomics

Applying spatial transcriptomics (ST) to analyze thrombi represents a novel approach, addressing the challenges posed by their amorphous nature and the difficulty in distinguishing components intrinsic to thrombus versus those from systemic components.Primarily used in oncology, the application of ST in stroke research is relatively unexplored. 1 In this study, we used ST to localize gene expression within thrombi, an approach that offers a distinct advantage over traditional bulk sequencing, which lacks the resolution to detect regional variations within complex tissues.Despite its higher cost, ST allows for detailed mapping of gene expression patterns within discrete Regions of Interest (ROIs), enabling observation of the molecular dynamics in different parts of a thrombus.ST examines the spatial distribution and molecular composition within their native environment, revealing gene expression patterns and pathways that may differentiate regions prone to causing deleterious effects such as distal embolization, inflammation, or resistance to thrombolytics.Further development of ST may help identify previously unrecognized therapeutic targets or subtype-specific biomarkers in acute ischemic stroke (AIS).Arterial thrombi from four AIS patients were analyzed, comprising two males and two females aged 75 to 89 years, with diverse ethnic backgrounds.All subjects received intravenous lytics.Stroke subtypes were determined as large artery atherosclerosis (LAA) or cardioembolic (CE) using TOAST criteria.2 Thrombi were retrieved during standard thrombectomy from the middle cerebral artery using a triaxial system, ensuring intact