scFFPE-ATAC enables high-throughput single cell chromatin accessibility profiling in formalin-fixed paraffin-embedded samples.
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Yadav RP, Xing P, Zhao M, Hollander P, Strell C, Xie M, Salehi M, Torell E, Sjöblom T, Enblad G, Amini RM, Swartling FJ, Glimelius I, Micke P, Hellström M, Chen X
Nat Commun 16 (1) 10022 [2025-11-14; online 2025-11-14]
Formalin-fixed paraffin-embedded (FFPE) samples are the gold standard for tissue preservation in clinical and research settings. Current single-cell chromatin accessibility technologies cannot resolve cell-type-specific epigenetic profiles in FFPE tissues due to extensive DNA damage. We present scFFPE-ATAC, a high-throughput single-cell chromatin accessibility assay for FFPE samples that integrates an FFPE-adapted Tn5 transposase, ultra-high-throughput DNA barcoding (>56 million barcodes per run), T7 promoter-mediated DNA damage repair, and in vitro transcription. We benchmark scFFPE-ATAC on FFPE mouse spleen and validate its performance against fresh tissue. We apply it to human lymph node samples archived for 8-12 years and to lung cancer FFPE tissues, revealing distinct regulatory trajectories between tumor center and invasive edge. Analysis of archived follicular lymphoma and transformed diffuse large B-cell lymphoma samples identifies relapse- and transformation-associated epigenetic dynamics. scFFPE-ATAC enables retrospective, spatial, and mechanistic epigenetic studies in long-term archived specimens.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 41238550
DOI 10.1038/s41467-025-66170-4
Crossref 10.1038/s41467-025-66170-4
pii: 10.1038/s41467-025-66170-4
pmc: PMC12618699