scFFPE-ATAC for high-throughput single cell chromatin accessibility profiling in formalin-fixed paraffin-embedded samples v1

Formalin-fixed paraffin-embedded (FFPE) samples are the gold standard for tissue preservation in both clinical practice and biomedical research. Chromatin accessibility governs gene expression by modulating the interaction between transcription factors and DNA. Current single-cell chromatin accessibility profiling technology fails to resolve cell-type-specific epigenetic profiles in FFPE samples due to extensive DNA damage. To address this technological gap, we introduce scFFPE-ATAC, an innovative, high-throughput single-cell chromatin accessibility assay for FFPE samples. scFFPE-ATAC integrates a newly engineered FFPE-Tn5 transposase, ultra-high-throughput DNA barcoding (>56 million cell barcodes per run), T7 promoter-mediated DNA damage rescue, and in vitro transcription. Our simple step-by-step workflow makes possible single cell chromatin profiling of FFPE archived biological samples.