What is Stereo-seq? Revolutionizing Spatial Transcriptomics with Unmatched Resolution and Scale

Learn how Spatio-Temporal Enhanced Resolution Omics sequencing (Stereo-seq) enables unmatched access to the spatial transcriptome.

What is Stereo-seq?

Stereo-seq is a cutting-edge spatial transcriptomics technology at the core of all Complete Genomics spatial biology solutions. This innovative approach enables researchers provides a powerful tool for understanding complex biological processes at the molecular level.

At the highest level, Stereo-seq combines next-generation sequencing with in situ RNA capture to map the spatial distribution of RNA transcripts within tissues. Featured on the cover of Cell in 2022, Stereo-seq offers unprecedented insights into gene expression patterns across large tissue areas with subcellular resolution.

Key Features of Stereo-seq Technology

Nanoscale Resolution Meets Large-Scale Tissue Analysis

Stereo-seq achieves a remarkable spatial resolution of 500 nm, allowing for the identification and localization of single cells and their molecular information.

This nanoscale precision combined with the ability to analyze large tissue areas, enables researchers to capture fine cellular details and broad tissue-wide patterns in a single experiment.

Unbiased Whole-Transcriptome Profiling

As a sequencing-based method, Stereo-seq captures polyadenylated RNA transcripts across the entire transcriptome without pre-selection of genes.

This unbiased approach allows for the discovery of novel gene expression patterns and cellular states that targeted approaches might miss.

DNA Nanoball Technology

At the heart of Stereo-seq is its innovative use of DNBSEQ™ technology, DNA nanoball (DNB) patterned arrays to achieve high-resolution spatial barcoding.

This technology enables the precise capture and localization of RNA molecules within the tissue sample.

Benefits of Stereo-seq Technology

True Single-cell Resolution

Stereo-seq technology offers researchers a novel tool to explore spatial biology with unprecedented true single cell resolution at 0.5 µm. It enables simultaneous transcriptome study and analysis at tissue, cellular, subcellular, and molecular levels.

Large Capture Area

Stereo-Seq accommodates larger tissue samples by offering a centimeter-level field of view.

The standard frame is 1 cm x 1 cm and can be expanded to 13 cm x 13 cm for interrogating whole mammalian embryos, human organs, or model organisms.

Tissue Type Compatible and Species Agnostic

Stereo-seq technology supports diverse tissue preparations, including fresh/fixed, frozen, and FFPE samples.

The poly-adenylated mRNA capture method supports a wide range of tissues and species, including humans, animals, and plants.

How Does Stereo-seq Work?

1. Stereo-seq uses DNA nanoballs (DNBs) as its foundational technology. DNBs are created during library preparation, during which single-stranded circular DNA (sscirDNA) molecules are created.
2. With the sscirDNA as a template, rolling circle replication (RCR) creates billions of DNBs in a single tube.
3. DNBs are loaded onto DNA nanoball patterned arrays to achieve high-resolution spatial barcoding. Barcodes serve as coordinate IDs to map sequences to a location.
4. Our DNBSEQ platforms then read the spatial barcodes, which are key to mapping sequenced transcripts back to their original locations on the Stereo-seq array

Essentially, the DNBSEQ platform serves as the engine that powers Stereo-seq by providing the high-throughput, high-quality sequencing necessary to capture and analyze spatial gene expression data across large tissue areas with high resolution.

How Does Stereo-Seq Compare to Other Methods?

A review of sequencing-based spatial transcriptomics methodologies demonstrated that Stereo-seq stands out for its large field of view, high sensitivity, and potential for subcellular resolution.

This makes Stereo-seq particularly suitable for studies requiring comprehensive spatial gene expression analysis across large tissue areas. Learn more in the Nature 2024 article Systematic comparison of sequencing-based spatial transcriptomic methods.