Decoder-FFPE-seq enables sensitive, genome-wide spatial transcriptomics of archival tissues at single-cell resolution
4 affiliations
- 1Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Urology, Department of pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
- 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430079, China.
- 3The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, State Key Laboratory of Physical Chemical of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
- 4Suzhou Dynamic Biosystems Co. Ltd., Suzhou 215200, China.
Abstract
Formalin-fixed paraffin-embedded (FFPE) tissue-compatible spatial transcriptomics (ST) is transforming biology and histopathology, but achieving high sensitivity, genome-wide coverage, single-cell resolution, and researcher accessibility remains challenging. To address these challenges, we here present a dendrimeric DNA coordinate barcoding design for FFPE tissue-adapted spatial RNA sequencing (Decoder-FFPE-seq) by integrating RNA-to-DNA probe conversion with blotting-assisted barcoding. Decoder-FFPE-seq provides single-cell resolution with a >2.6-fold sensitivity increase in whole-transcriptome mouse brain and archived human sample profiling over existing platforms, resolving potential cellular identity of low-abundance genes, finer tissue architecture, and capturing an epithelial-mesenchymal transition-associated signature for prognostic value. With expanded probe libraries, Decoder-FFPE-seq captures long noncoding and viral RNAs, revealing their spatial coregulatory networks with messenger RNAs in oral squamous cell carcinomas (OSCCs). In an OSCC immunotherapy cohort, two CD8⁺ T cell subpopulations were respectively identified in pre- and postchemoimmunotherapy samples, potentially linked to treatment response. Decoder-FFPE-seq establishes a robust, high-resolution, and accessible framework for sensitive ST profiling of archival tissues in fundamental and translational studies.
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BibTeX
@article{cao2026decoderffpeseq,
title = {{Decoder-FFPE-seq enables sensitive, genome-wide spatial transcriptomics of archival tissues at single-cell resolution}},
author = {Jiao Cao and Jun Zeng and Yiwei Meng and Shanqing Huang and Jing Zhang and Xing Fang and Yang Guo and Weixiong Shi and Yutong Liu and Zhong Zheng and Jianchen Fang and Xuepeng Xiong and Gang Chen and Lingling Wu and Chaoyong Yang},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.ady5085},
url = {https://www.science.org/doi/abs/10.1126/sciadv.ady5085},
note = {CC BY},
}
RIS
TY - JOUR
TI - Decoder-FFPE-seq enables sensitive, genome-wide spatial transcriptomics of archival tissues at single-cell resolution
AU - Jiao Cao
AU - Jun Zeng
AU - Yiwei Meng
AU - Shanqing Huang
AU - Jing Zhang
AU - Xing Fang
AU - Yang Guo
AU - Weixiong Shi
AU - Yutong Liu
AU - Zhong Zheng
AU - Jianchen Fang
AU - Xuepeng Xiong
AU - Gang Chen
AU - Lingling Wu
AU - Chaoyong Yang
PY - 2026
DA - 2026/10/30
JO - Science Advances
DO - 10.1126/sciadv.ady5085
UR - https://www.science.org/doi/abs/10.1126/sciadv.ady5085
AB - Formalin-fixed paraffin-embedded (FFPE) tissue-compatible spatial transcriptomics (ST) is transforming biology and histopathology, but achieving high sensitivity, genome-wide coverage, single-cell resolution, and researcher accessibility remains challenging. To address these challenges, we here present a dendrimeric DNA coordinate barcoding design for FFPE tissue-adapted spatial RNA sequencing (Decoder-FFPE-seq) by integrating RNA-to-DNA probe conversion with blotting-assisted barcoding. Decoder-FFPE-seq provides single-cell resolution with a >2.6-fold sensitivity increase in whole-transcriptome mouse brain and archived human sample profiling over existing platforms, resolving potential cellular identity of low-abundance genes, finer tissue architecture, and capturing an epithelial-mesenchymal transition-associated signature for prognostic value. With expanded probe libraries, Decoder-FFPE-seq captures long noncoding and viral RNAs, revealing their spatial coregulatory networks with messenger RNAs in oral squamous cell carcinomas (OSCCs). In an OSCC immunotherapy cohort, two CD8⁺ T cell subpopulations were respectively identified in pre- and postchemoimmunotherapy samples, potentially linked to treatment response. Decoder-FFPE-seq establishes a robust, high-resolution, and accessible framework for sensitive ST profiling of archival tissues in fundamental and translational studies.
SN - 2375-2548
ER -