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Comprehensive Spatial Profiling of Species-agnostic Transcriptomes via Stereo-seq
Published on: October 31, 2025
Spatial Total RNA Sequencing of Formalin-Fixed Paraffin-Embedded Tissue by spRandom-seq
Yuan Liao1,2, Jiaye Chen1, Shunji Zhang3
1Department of Laboratory Medicine of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Small (Weinheim an Der Bergstrasse, Germany)
|July 21, 2026
Summary
spRandom-seq enables spatial total RNA sequencing in FFPE tissues, revealing host, bacterial, and viral transcriptomes. This technology maps transcriptional heterogeneity in cancer and infections for clinical pathology applications.
Area of Science:
- Molecular Biology
- Genomics
- Pathology
Background:
- Host and microbial RNA transcripts orchestrate disease pathogenesis at the nanoscale within tissue microenvironments.
- Spatially resolving comprehensive transcriptional landscapes in complex clinical tissues like FFPE specimens remains challenging.
Purpose of the Study:
- To introduce spRandom-seq, a novel spatial total RNA sequencing technology.
- To enable spatial resolution of complete transcriptomes from host, bacteria, and viruses in FFPE tissues.
Main Methods:
- Development of spRandom-seq, a random primer-based spatial total RNA sequencing technology.
- Application of spRandom-seq to mouse brain, olfactory bulb, and clinical FFPE sections (breast cancer, Klebsiella pneumoniae infection, HBV-positive HCC).
Main Results:
- spRandom-seq identified lncRNAs and alternative splicing events in mouse tissues.
- Spatial heterogeneity was delineated in breast cancer and microbial infection sites.
- Integrated analysis of host and viral RNAs in HBV-positive HCC revealed specific activation of complement and coagulation pathways and increased CNVs in infected tumor areas.
Conclusions:
- spRandom-seq is a practical and scalable approach for spatial transcriptomics in FFPE tissues.
- The technology is compatible with existing platforms and has minimal operational complexity.
- spRandom-seq holds promise for clinical pathology applications and infection diagnostics.
