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<p>While formalin-fixed paraffin-embedded (FFPE) samples are invaluable for human non-Hodgkin B-cell lymphoma translational research, effective methods for spatial profiling of chromatin accessibility and histone modifications in these tissues remain limited. Here, we introduce epi-Patho-DBiT, a platform that combines reverse crosslinking of FFPE tissues with spatially resolved assays for transposase-accessible chromatin using sequencing (spatial-FFPE-ATAC) or cleavage under targets and tagmentation (spatial-FFPE-CUT&amp;Tag). Using spatial-FFPE-ATAC, we map epigenetic landscapes in mucosa-associated lymphoid tissue and follicular lymphoma, identifying chromatin variants linked to B-cell malignancy and resolving tumor karyotypes. Mitotic age inference reveals spatial tumor dynamics and uncovers cholesterol-mediated cell proliferation. Furthermore, spatial-FFPE-CUT&amp;Tag elucidates genomic alterations during transformation of follicular lymphoma into diffuse large B-cell lymphoma and identifies <i>DIP2C</i> with dysregulated H3K4me3 and H3K27me3 levels. Unexpectedly, we observe elevated H3K27me3 occupancy at a chromosome 2 locus containing tumor-promoting genes, attributed to copy number amplification and thereby upregulation in transformed diffuse large B-cell lymphoma.</p>

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Spatially decoding genotype-associated epigenetic landscapes in human lymphoma FFPE tissues via epi-Patho-DBiT

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月1日

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  • Haikuo Li,
  • Bo Tao,
  • Archibald Enninful,
  • Dingyao Zhang,
  • Yi Dai,
  • Fiona Oh,
  • Negin Farzad,
  • Keyi Li,
  • Zhiliang Bai,
  • Xiaoyu Qin,
  • Mingyu Yang,
  • Emily J. Hwang,
  • Jing Zhang,
  • Jun Lu,
  • Mark Gerstein,
  • Jingtian Zhou,
  • Mina L. Xu,
  • Rong Fan

摘要

While formalin-fixed paraffin-embedded (FFPE) samples are invaluable for human non-Hodgkin B-cell lymphoma translational research, effective methods for spatial profiling of chromatin accessibility and histone modifications in these tissues remain limited. Here, we introduce epi-Patho-DBiT, a platform that combines reverse crosslinking of FFPE tissues with spatially resolved assays for transposase-accessible chromatin using sequencing (spatial-FFPE-ATAC) or cleavage under targets and tagmentation (spatial-FFPE-CUT&Tag). Using spatial-FFPE-ATAC, we map epigenetic landscapes in mucosa-associated lymphoid tissue and follicular lymphoma, identifying chromatin variants linked to B-cell malignancy and resolving tumor karyotypes. Mitotic age inference reveals spatial tumor dynamics and uncovers cholesterol-mediated cell proliferation. Furthermore, spatial-FFPE-CUT&Tag elucidates genomic alterations during transformation of follicular lymphoma into diffuse large B-cell lymphoma and identifies DIP2C with dysregulated H3K4me3 and H3K27me3 levels. Unexpectedly, we observe elevated H3K27me3 occupancy at a chromosome 2 locus containing tumor-promoting genes, attributed to copy number amplification and thereby upregulation in transformed diffuse large B-cell lymphoma.