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Related Experiment Video

Updated: Oct 18, 2025

Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
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SEAM is a spatial single nuclear metabolomics method for dissecting tissue microenvironment.

Zhiyuan Yuan1, Qiming Zhou2, Lesi Cai3

  • 1MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, BNRist, Institute of TCM-X, Department of Automation, Tsinghua University, Beijing, China.

Nature Methods
|October 5, 2021
PubMed
Summary

Spatial single nuclear metabolomics (SEAM) reveals metabolic fingerprints in single cells. This method maps metabolic zonation in mouse liver and identifies unique hepatocyte features in human fibrotic liver tissue.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Tissue Engineering

Background:

  • Spatial metabolomics offers insights into cellular heterogeneity and tissue structure.
  • Understanding metabolic organization is crucial for deciphering tissue function and disease pathology.

Purpose of the Study:

  • To introduce a novel method, spatial single nuclear metabolomics (SEAM), for high-resolution spatial metabolic profiling.
  • To investigate metabolic zonation in mouse liver and spatial metabolic profiles in human fibrotic liver.

Main Methods:

  • Developed SEAM, integrating high-spatial-resolution imaging mass spectrometry with computational algorithms.
  • Applied SEAM to wild-type mouse tissues and human fibrotic liver samples.
  • Validated findings using spatial transcriptomics (Geo-seq).

Main Results:

  • Delineated a consistent metabolic zonation pattern in mouse liver tissue.
  • Identified distinct hepatocyte subpopulations with unique metabolic features in proximity to fibrotic niches in human liver.
  • Demonstrated SEAM's capability for single-cell level metabolic and histological analysis.

Conclusions:

  • SEAM provides a powerful platform for exploring spatial metabolic landscapes at single-cell resolution.
  • The study deepens the understanding of tissue metabolic organization and its alterations in fibrotic diseases.
  • SEAM facilitates the discovery of cell-specific metabolic characteristics within complex tissue microenvironments.