Guo Pengfei, Chen Yufan, Mao Liran, Cardilla Angelysia, Lee Chin Nien, Cui Yan, Jin Dengge, Hua Yucong, Xu Xiaowei, Deng Yanxiang
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Nat Commun. 2025 Jul 1;16(1):5945. doi: 10.1038/s41467-025-60882-3.
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.
福尔马林固定石蜡包埋（FFPE）样本是表观基因组学研究中一个巨大的、尚未开发的资源，但用于深入分析这些样本的分子工具仍然有限。我们引入了空间FFPE-ATAC-seq，这是一种用于在存档组织中进行染色质可及性原位分析的方法。这种方法克服了福尔马林诱导的交联挑战，能够在保留组织结构的同时对染色质景观进行高分辨率映射。将空间FFPE-ATAC-seq应用于小鼠和人类组织，包括脑和胸腺，揭示了与组织形态一致的复杂空间组织和不同细胞类型。与单细胞RNA测序相结合，验证了我们的染色质图谱在识别关键细胞类型和调控元件方面的准确性。我们进一步将该方法应用于人类黑色素瘤，全面表征肿瘤和非肿瘤区域的染色质可及性。该方法显著扩展了表观基因组学研究的工具包，释放了大量存档FFPE样本在空间背景下研究基因调控和疾病机制的潜力。
