Spatial Multiomics in Frozen Tissue Sections: Sample Preparation Matters

Spatial biology is rapidly changing how researchers study complex tissues. Instead of looking only at which genes are expressed, spatial approaches preserve positional information, helping researchers connect molecular signals with tissue architecture, cell identity, and local cell-cell interactions.

A recent JoVE protocol from Zhang et al. at Mayo Clinic presents a spatially resolved single-cell multiomic workflow for frozen tissue sections. The method combines spatial barcoding with single-cell profiling of both gene expression and the H3K27ac epigenomic mark, enabling transcriptomic and regulatory information to be assigned back to anatomical coordinates in the tissue.

In the workflow, high-quality nuclei isolation is a critical step. The authors describe gentle tissue dissociation and nuclei purification using Invent Minute single-nucleus isolation kit for neuronal tissues/cells (BN-020). The protocol highlights several key nuclei quality control factors, including yield, nuclear integrity, aggregation, and debris content.

This is exactly where sample preparation can make or break advanced spatial and single-cell assays. For workflows such as single-nucleus RNA-seq, ATAC-seq, CUT&Tag, and emerging spatial multiomic methods, intact and well-separated nuclei help support cleaner downstream data and more reliable biological interpretation.

As spatial biology continues to expand from transcriptomics into integrated epigenomic and multiomic profiling, robust nuclei preparation will remain a foundational part of the workflow. We are excited to see Invent Biotechnologies products supporting researchers working at the front edge of spatial biology.

Reference: Zhang et al. “Spatially Resolved, Integrated Single-Cell Multiomic Profiling of the Transcriptome and Epigenomic Targets in Frozen Tissue Sections.” Journal of Visualized Experiments, 2026. DOI: 10.3791/71046.