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A quantitative spatial cell-cell colocalizations framework enabling comparisons between in vitro assembloids and pathological specimens

Author

Listed:
  • Gina Bouchard

    (Stanford University)

  • Weiruo Zhang

    (Stanford University)

  • Ilayda Ilerten

    (Stanford University)

  • Irene Li

    (Stanford University)

  • Asmita Bhattacharya

    (Stanford University)

  • Yuanyuan Li

    (Stanford University)

  • Winston Trope

    (Stanford University)

  • Joseph B. Shrager

    (Stanford University
    Veterans Affairs Palo Alto Health Care System)

  • Calvin Kuo

    (Stanford University)

  • Michael G. Ozawa

    (Stanford University)

  • Amato J. Giaccia

    (Stanford University
    University of Oxford)

  • Lu Tian

    (Stanford University)

  • Sylvia K. Plevritis

    (Stanford University
    Stanford University)

Abstract

Spatial omics is enabling unprecedented tissue characterization, but the ability to adequately compare spatial features across samples under different conditions is lacking. We propose a quantitative framework that catalogs significant, normalized, colocalizations between pairs of cell subpopulations, enabling comparisons among a variety of biological samples. We perform cell-pair colocalization analysis on multiplexed immunofluorescence images of assembloids constructed with lung adenocarcinoma (LUAD) organoids and cancer-associated fibroblasts derived from human tumors. Our data show that assembloids recapitulate human LUAD tumor-stroma spatial organization, justifying their use as a tool for investigating the spatial biology of human disease. Intriguingly, drug-perturbation studies identify drug-induced spatial rearrangements that also appear in treatment-naïve human tumor samples, suggesting potential directions for characterizing spatial (re)-organization related to drug resistance. Moreover, our work provides an opportunity to quantify spatial data across different samples, with the common goal of building catalogs of spatial features associated with disease processes and drug response.

Suggested Citation

  • Gina Bouchard & Weiruo Zhang & Ilayda Ilerten & Irene Li & Asmita Bhattacharya & Yuanyuan Li & Winston Trope & Joseph B. Shrager & Calvin Kuo & Michael G. Ozawa & Amato J. Giaccia & Lu Tian & Sylvia K, 2025. "A quantitative spatial cell-cell colocalizations framework enabling comparisons between in vitro assembloids and pathological specimens," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55129-6
    DOI: 10.1038/s41467-024-55129-6
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    References listed on IDEAS

    as
    1. Loukia G. Karacosta & Benedict Anchang & Nikolaos Ignatiadis & Samuel C. Kimmey & Jalen A. Benson & Joseph B. Shrager & Robert Tibshirani & Sean C. Bendall & Sylvia K. Plevritis, 2019. "Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Yi-Ing Chen & Chin-Chun Chang & Min-Fen Hsu & Yung-Ming Jeng & Yu-Wen Tien & Ming-Chu Chang & Yu-Ting Chang & Chun-Mei Hu & Wen-Hwa Lee, 2022. "Homophilic ATP1A1 binding induces activin A secretion to promote EMT of tumor cells and myofibroblast activation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
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