️ Episode 202: Stereo-seq V2: Spatial Total RNA Mapping in FFPE Tissues

In this episode of PaperCast Base by Base, we explore how Stereo-seq V2 delivers high-resolution spatial mapping of total RNA in FFPE samples, from mouse brain to breast cancer and tuberculosis lung tissue.

Study Highlights:
The authors introduce Stereo-seq V2, a random-priming spatial transcriptomics platform that captures total RNA in situ on FFPE sections at single-cell resolution. By benchmarking against earlier Stereo-seq and other spatial methods in the mouse brain, they demonstrate improved gene detection, uniform gene body coverage, and robust profiling of non-coding RNAs and immune receptor transcripts. In long-stored triple-negative breast cancer blocks, Stereo-seq V2 maintains high sensitivity despite degraded RNA, enabling inference of copy-number alterations and spatially resolved alternative splicing events that distinguish tumor subtypes. Using Mycobacterium tuberculosis infection models in mice and human lung tissue, the study simultaneously maps host and pathogen transcriptomes and reconstructs spatial B cell receptor repertoires, revealing clonal expansion and affinity maturation around necrotic lesions.

Conclusion:
Stereo-seq V2 unlocks archival FFPE samples for high-resolution spatial total RNA and immune repertoire analysis, opening new avenues for translational research, infectious disease biology, and precision pathology.

Music:
Enjoy the music based on this article at the end of the episode.

Reference:
Zhao Y, Li Y, He Y, et al. (2025) Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution. Cell 188, 6554–6571. https://doi.org/10.1016/j.cell.2025.08.008

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.