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Abstract
Background Advances in spatial transcriptomic technologies have led to a greater understanding of the complexity of cellular interactions in development and disease. Technologies with increased spatial resolution are required to more precisely distinguish and characterize cellular diversity and disease states within tissues.The Visium HD Spatial Gene Expression assay is a novel, high-resolution spatial technology that utilizes a whole transcriptome probe panel and resolves data at single-cell scale within intact tissue sections. Our Visium HD array consists of a grid with 2 x 2 µm barcoded areas, and the data is binned to 8 x 8 µm for analysis.
Methods To demonstrate the capabilities of the Visium HD assay, we applied it on formalin-fixed, paraffin embedded (FFPE) human breast cancer, a tissue with high clinical relevance as well as complex spatial organization and cellular composition. Tissue sections mounted on standard glass slides are stained with Hematoxylin & Eosin (H&E) and imaged prior to the Visium HD workflow, allowing for morphological assessment to be performed upstream of single-cell scale whole transcriptomic profiling from the same tissue section.
Results Using Visium HD, several important cell types were identified at their expected spatial localizations. Based on unbiased clustering and marker gene expression, we located several major cell types, such as EPCAM+ breast epithelial cells that were further resolved into basal (KRT14+) and luminal (KRT18+) cells, many immune cell populations (MS4A+ B cells, JCHAIN+ plasma cells, CD3D+ T cells, CD68+ macrophages), PECAM1+ endothelial cells and COL1A1+ and VIM+ stromal cells.
Conclusions The Visium HD transcriptomic analysis provided insights into the cellular heterogeneity and organization within human breast cancer at single-cell scale resolution. The Visium platform enables researchers to gain novel insights on normal development, disease pathology, and clinical translational research. Visium HD will further these capabilities and expand biological applications.
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