Beyond Sequencing: The Spatial Dimensions of the Transcriptome

The integration of sequencing and spatial technologies is becoming more prevalent, underscoring the need to understand the evolving spatial landscape. In this article, we’ll review the various spatial transcriptomics tools and techniques, spotlighting sequencing-based and image-based solutions from leading organizations in the field.


Technology: Originating from a Harvard University spin-out, Vizgen evolved the core MERFISH (Multiplexed Error-Robust Fluorescence in situ Hybridization) technology1 from the Zhuang lab to create their MERSCOPE Platform. This refined method allows for advanced spatial transcriptomics in native tissues, enabling the analysis of up to 500 genes within single cells.

How it works: MERFISH expands upon smFISH (single-molecule fluorescence in situ hybridization)2,3 by utilizing combinatorial labeling, multiple rounds of imaging, and error-robust barcoding. During this process, each gene is given a unique binary barcode, which is read out through the binding of specific probes to their targeted genes. After multiple rounds of imaging, these barcodes are read by observing fluorescence patterns, producing high-resolution spatial identification and quantification of diverse RNA species.

Highlights: Terry Lo, CEO and President of Vizgen, emphasized the importance of data quality in their work, stating, “Our strengths are in the data quality.” He outlined several primary benefits of their MERFISH technology. First, employing multiple probes against a single target ensures a stronger signal and improved specificity. Lo also stressed the value of combinatorial barcoding. Through successive rounds of imaging, this feature increases multiplexing far beyond what typical imaging techniques can offer. Finally, these barcodes serve as an “error-robust” feature, which prevents optical crowding and aids in error correction. Complementing their offerings, Vizgen provides a custom Gene Panel Design software, allowing researchers to tailor their studies to specific genes.

Recent advances: In addition to their custom gene panels, Vizgen introduced the MERSCOPE PanNeuro Cell Type Predesigned Panel, a 500-gene tool that identifies and explores major cell types, subtypes, and interactions in the mouse brain. They also released the MERSCOPE PanCancer Pathways Panel, a gene list targeting key cancer signaling pathways and designed to identify both healthy and disease states across various cancer types. During AGBT 2023, Vizgen announced plans to increase their multiplexing capabilities to allow the analysis of up to 1,000 genes at high resolution.