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Updated: May 27, 2025

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Seq-Scope-eXpanded: Spatial Omics Beyond Optical Resolution.

Angelo Anacleto1, Weiqiu Cheng2, Qianlu Feng3,4

  • 1Department of Molecular & Integrative Physiology, University of Michigan.

Biorxiv : the Preprint Server for Biology
|February 20, 2025
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Summary
This summary is machine-generated.

Seq-Scope-X enhances spatial transcriptomics (sST) by expanding tissues, achieving submicrometer resolution. This breakthrough reveals cellular compartment gene expression differences and enables spatial proteomic analysis.

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Area of Science:

  • Spatial biology
  • Genomics
  • Molecular imaging

Background:

  • Sequencing-based spatial transcriptomics (sST) offers transcriptome-wide gene expression mapping.
  • Current sST methods lack the optical resolution of imaging-based techniques (200-300 nm).
  • Transcript diffusion limits spatial precision in existing sST approaches.

Purpose of the Study:

  • To enhance Seq-Scope's submicrometer resolution using tissue expansion.
  • To overcome the resolution limitations of current sST methods.
  • To enable ultra-high-resolution whole-transcriptome and proteome profiling.

Main Methods:

  • Development of Seq-Scope-X (Seq-Scope-eXpanded) utilizing physical tissue enlargement.
  • Minimizing transcript diffusion effects through tissue expansion.
  • Applying Seq-Scope-X to liver, brain, and colon tissues for transcriptomic analysis.
  • Modifying Seq-Scope-X for spatial proteomic analysis using barcode-tagged antibodies.

Main Results:

  • Seq-Scope-X achieved submicrometer resolution, surpassing previous sST limitations.
  • Tissue expansion increased spatial feature density by an order of magnitude.
  • Resolved nuclear and cytoplasmic compartments in nearly all liver cells, revealing distinct transcriptome patterns.
  • Demonstrated dynamic metabolic role switching in hepatocytes, confirmed by imaging methods.
  • Successfully applied to non-hepatic tissues and adapted for spatial proteomic profiling.

Conclusions:

  • Seq-Scope-X is a transformative tool for ultra-high-resolution spatial transcriptomics and proteomics.
  • The technology provides unparalleled spatial precision for cellular analysis.
  • Findings advance understanding of cellular architecture, function, and disease mechanisms.
  • Revealed significant nuclear-cytoplasmic transcriptome differences impacting cell function.