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Spatial profiling of chromatin accessibility in formalin-fixed paraffin-embedded tissues

Author

Listed:
  • Pengfei Guo

    (University of Pennsylvania)

  • Yufan Chen

    (University of Pennsylvania)

  • Liran Mao

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Angelysia Cardilla

    (University of Pennsylvania)

  • Chin Nien Lee

    (University of Pennsylvania)

  • Yan Cui

    (Whitehead Institute for Biomedical Research)

  • Dengge Jin

    (University of Pennsylvania)

  • Yucong Hua

    (University of Pennsylvania)

  • Xiaowei Xu

    (University of Pennsylvania)

  • Yanxiang Deng

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

Abstract

Formalin-fixed paraffin-embedded (FFPE) samples represent a vast, untapped resource for epigenomic research, yet molecular tools for deep analysis of these specimens remain limited. We introduce spatial FFPE-ATAC-seq, an approach for in situ profiling chromatin accessibility within archived tissues. This approach overcomes formalin-induced crosslinking challenges, allowing high-resolution mapping of chromatin landscapes while preserving tissue architecture. Applying spatial FFPE-ATAC-seq to mouse and human tissues, including brain and thymus, reveals intricate spatial organization and distinct cell types in alignment with tissue morphology. Integration with single-cell RNA sequencing validates the precision of our chromatin profiles in identifying key cell types and regulatory elements. We further apply this method to human melanoma, comprehensively characterizing chromatin accessibility across both tumor and non-tumor regions. This method significantly expands the toolkit for epigenomic research, unlocking the potential of an extensive collection of archived FFPE samples for studying gene regulation and disease mechanisms with spatial context.

Suggested Citation

  • Pengfei Guo & Yufan Chen & Liran Mao & Angelysia Cardilla & Chin Nien Lee & Yan Cui & Dengge Jin & Yucong Hua & Xiaowei Xu & Yanxiang Deng, 2025. "Spatial profiling of chromatin accessibility in formalin-fixed paraffin-embedded tissues," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60882-3
    DOI: 10.1038/s41467-025-60882-3
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    References listed on IDEAS

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    1. Yang Eric Li & Sebastian Preissl & Xiaomeng Hou & Ziyang Zhang & Kai Zhang & Yunjiang Qiu & Olivier B. Poirion & Bin Li & Joshua Chiou & Hanqing Liu & Antonio Pinto-Duarte & Naoki Kubo & Xiaoyu Yang &, 2021. "An atlas of gene regulatory elements in adult mouse cerebrum," Nature, Nature, vol. 598(7879), pages 129-136, October.
    2. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    3. Suijuan Zhong & Mengdi Wang & Luwei Huang & Youqiao Chen & Yuxin Ge & Jiyao Zhang & Yingchao Shi & Hao Dong & Xin Zhou & Bosong Wang & Tian Lu & Xiaoxi Jing & Yufeng Lu & Junjing Zhang & Xiaoqun Wang , 2023. "Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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