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Expanded vacuum-stable gels for multiplexed high-resolution spatial histopathology

Author

Listed:
  • Yunhao Bai

    (Stanford University
    Stanford University)

  • Bokai Zhu

    (Stanford University
    Stanford University)

  • John-Paul Oliveria

    (Genentech, Inc.
    McMaster University)

  • Bryan J. Cannon

    (Stanford University)

  • Dorien Feyaerts

    (Stanford University)

  • Marc Bosse

    (Stanford University)

  • Kausalia Vijayaragavan

    (Stanford University)

  • Noah F. Greenwald

    (Stanford University)

  • Darci Phillips

    (Stanford University)

  • Christian M. Schürch

    (Stanford University
    University Hospital and Comprehensive Cancer Center Tübingen)

  • Samuel M. Naik

    (Harvard Medical School)

  • Edward A. Ganio

    (Stanford University)

  • Brice Gaudilliere

    (Stanford University)

  • Scott J. Rodig

    (Harvard Medical School)

  • Michael B. Miller

    (Harvard Medical School
    Harvard Medical School
    Boston Children’s Hospital
    Broad Institute of MIT and Harvard)

  • Michael Angelo

    (Stanford University)

  • Sean C. Bendall

    (Stanford University)

  • Xavier Rovira-Clavé

    (Stanford University
    Stanford University)

  • Garry P. Nolan

    (Stanford University)

  • Sizun Jiang

    (Stanford University
    Broad Institute of MIT and Harvard
    Beth Israel Deaconess Medical Center
    Dana Farber Cancer Institute)

Abstract

Cellular organization and functions encompass multiple scales in vivo. Emerging high-plex imaging technologies are limited in resolving subcellular biomolecular features. Expansion Microscopy (ExM) and related techniques physically expand samples for enhanced spatial resolution, but are challenging to be combined with high-plex imaging technologies to enable integrative multiscaled tissue biology insights. Here, we introduce Expand and comPRESS hydrOgels (ExPRESSO), an ExM framework that allows high-plex protein staining, physical expansion, and removal of water, while retaining the lateral tissue expansion. We demonstrate ExPRESSO imaging of archival clinical tissue samples on Multiplexed Ion Beam Imaging and Imaging Mass Cytometry platforms, with detection capabilities of > 40 markers. Application of ExPRESSO on archival human lymphoid and brain tissues resolved tissue architecture at the subcellular level, particularly that of the blood-brain barrier. ExPRESSO hence provides a platform for extending the analysis compatibility of hydrogel-expanded biospecimens to mass spectrometry, with minimal modifications to protocols and instrumentation.

Suggested Citation

  • Yunhao Bai & Bokai Zhu & John-Paul Oliveria & Bryan J. Cannon & Dorien Feyaerts & Marc Bosse & Kausalia Vijayaragavan & Noah F. Greenwald & Darci Phillips & Christian M. Schürch & Samuel M. Naik & Edw, 2023. "Expanded vacuum-stable gels for multiplexed high-resolution spatial histopathology," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39616-w
    DOI: 10.1038/s41467-023-39616-w
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    References listed on IDEAS

    as
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