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<p>Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200–300 nm) of imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, Seq-Scope-X minimizes transcript diffusion effects and increases spatial feature density by an additional order of magnitude. In liver tissue, this approach resolves nuclear and cytoplasmic compartments in nearly every single cell, uncovering widespread differences between nuclear and cytoplasmic transcriptome patterns. Independently confirmed by imaging-based methods, these results suggest that individual hepatocytes can dynamically switch their metabolic roles. Seq-Scope-X also works in brain and colon, and can be adapted for spatial proteomics, profiling hundreds of barcode-tagged antibody stains at microscopic resolutions in mouse spleens and human tonsils. Together, these findings establish Seq-Scope-X as a powerful platform for ultra-high-resolution whole-transcriptome and proteome profiling, expanding the spatial precision achievable for studying cellular architecture, function, and disease mechanisms.</p>

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Seq-Scope-eXpanded: spatial omics beyond optical resolution

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月10日

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  • Angelo Anacleto,
  • Weiqiu Cheng,
  • Qianlu Feng,
  • Anna Park,
  • Chun-Seok Cho,
  • Yongha Hwang,
  • Yongsung Kim,
  • Yichen Si,
  • Jer-En Hsu,
  • Qingyang Zhao,
  • Xiaoya Zhao,
  • Daniel Kim,
  • Mitchell Schrank,
  • Alex William Schrader,
  • Seokjin Yeo,
  • Rosane Teles,
  • Robert L. Modlin,
  • Olesya Plazyo,
  • Johann E. Gudjonsson,
  • Myungjin Kim,
  • Chang H. Kim,
  • Hee-Sun Han,
  • Hyun Min Kang,
  • Jun Hee Lee

摘要

Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200–300 nm) of imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, Seq-Scope-X minimizes transcript diffusion effects and increases spatial feature density by an additional order of magnitude. In liver tissue, this approach resolves nuclear and cytoplasmic compartments in nearly every single cell, uncovering widespread differences between nuclear and cytoplasmic transcriptome patterns. Independently confirmed by imaging-based methods, these results suggest that individual hepatocytes can dynamically switch their metabolic roles. Seq-Scope-X also works in brain and colon, and can be adapted for spatial proteomics, profiling hundreds of barcode-tagged antibody stains at microscopic resolutions in mouse spleens and human tonsils. Together, these findings establish Seq-Scope-X as a powerful platform for ultra-high-resolution whole-transcriptome and proteome profiling, expanding the spatial precision achievable for studying cellular architecture, function, and disease mechanisms.