{ "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.", "abstract_shown": true, "affiliations": [ "Institute 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.", "State 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.", "The 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.", "Suzhou Dynamic Biosystems Co. Ltd., Suzhou 215200, China." ], "article_type": "Research Article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0 ], "name": "Jiao Cao", "orcid": "0000-0002-9596-5723" }, { "affs": [ 1 ], "name": "Jun Zeng", "orcid": "0009-0002-3229-6718" }, { "affs": [ 0 ], "name": "Yiwei Meng", "orcid": "0000-0003-0112-1472" }, { "affs": [ 0, 2 ], "name": "Shanqing Huang" }, { "affs": [ 0, 2 ], "name": "Jing Zhang", "orcid": "0000-0002-2193-0149" }, { "affs": [ 3 ], "name": "Xing Fang" }, { "affs": [ 3 ], "name": "Yang Guo", "orcid": "0009-0004-7942-8567" }, { "affs": [ 0, 2 ], "name": "Weixiong Shi", "orcid": "0009-0007-3011-3208" }, { "affs": [ 1 ], "name": "Yutong Liu" }, { "affs": [ 0 ], "name": "Zhong Zheng", "orcid": "0000-0002-3500-9510" }, { "affs": [ 0 ], "name": "Jianchen Fang", "orcid": "0000-0002-6382-2680" }, { "affs": [ 1 ], "name": "Xuepeng Xiong", "orcid": "0000-0003-3519-9745" }, { "affs": [ 1 ], "name": "Gang Chen", "orcid": "0000-0003-3332-3511" }, { "affs": [ 0 ], "name": "Lingling Wu", "orcid": "0000-0001-8738-0357" }, { "affs": [ 0, 2 ], "name": "Chaoyong Yang", "orcid": "0000-0002-2374-5342" } ], "bibtex": "https://research.draconitic.com/paper/1kzy6ddx975sg.bib", "cited_by": 0, "doi": "10.1126/sciadv.ady5085", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721974/?tool=EBI", "id": "1kzy6ddx975sg", "issns": [ "2375-2548" ], "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.ady5085", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Biomedicine and Life Sciences" ], [ "heading", "Biophysics" ], [ "heading", "Life Sciences" ], [ "heading", "Research Article" ], [ "heading", "SciAdv r-articles" ] ], "openalex": null, "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721974/pdf/?tool=EBI", "pmcid": "PMC13721974", "pmid": "42962014", "published": "2026-10-30", "publisher": "American Association for the Advancement of Science (AAAS)", "ris": "https://research.draconitic.com/paper/1kzy6ddx975sg.ris", "sources": [ { "first_seen": "2026-10-31T00:20:30Z", "native_id": "10.1126/sciadv.ady5085", "source": "feed-science", "url": "https://www.science.org/doi/abs/10.1126/sciadv.ady5085" }, { "first_seen": "2026-10-31T00:20:32Z", "native_id": "10.1126/sciadv.ady5085", "source": "crossref", "url": "https://www.science.org/doi/10.1126/sciadv.ady5085" }, { "first_seen": "2026-10-31T12:21:37Z", "native_id": "PMC:PMC13721974", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13721974" }, { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42962014", "source": "europepmc", "url": "https://europepmc.org/article/MED/42962014" }, { "first_seen": "2026-11-03T12:22:34Z", "native_id": "PMC13721974", "source": "pmc", "url": "https://doi.org/10.1126/sciadv.ady5085" } ], "subjects": [ { "field": "biochemistry", "origin": "heading:Biophysics", "subfield": "biophysics" }, { "field": "biology", "origin": "heading:Life Sciences", "subfield": "general" } ], "title": "Decoder-FFPE-seq enables sensitive, genome-wide spatial transcriptomics of archival tissues at single-cell resolution", "title_text": "Decoder-FFPE-seq enables sensitive, genome-wide spatial transcriptomics of archival tissues at single-cell resolution", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:34Z", "url": "https://research.draconitic.com/paper/1kzy6ddx975sg", "venue": "Science Advances", "versions": [] }