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Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology

Author

Listed:
  • Thomas Hu

    (Georgia Institute of Technology and Emory University
    Georgia Institute of Technology)

  • Mayar Allam

    (Georgia Institute of Technology and Emory University)

  • Shuangyi Cai

    (Georgia Institute of Technology and Emory University)

  • Walter Henderson

    (Georgia Institute of Technology)

  • Brian Yueh

    (Cold Spring Harbor Laboratory)

  • Aybuke Garipcan

    (Cold Spring Harbor Laboratory)

  • Anton V. Ievlev

    (Center for Nanophase Materials Sciences)

  • Maryam Afkarian

    (University of California)

  • Semir Beyaz

    (Cold Spring Harbor Laboratory)

  • Ahmet F. Coskun

    (Georgia Institute of Technology and Emory University
    Georgia Institute of Technology
    Emory University
    Georgia Institute of Technology)

Abstract

Metabolic reprogramming in cancer and immune cells occurs to support their increasing energy needs in biological tissues. Here we propose Single Cell Spatially resolved Metabolic (scSpaMet) framework for joint protein-metabolite profiling of single immune and cancer cells in male human tissues by incorporating untargeted spatial metabolomics and targeted multiplexed protein imaging in a single pipeline. We utilized the scSpaMet to profile cell types and spatial metabolomic maps of 19507, 31156, and 8215 single cells in human lung cancer, tonsil, and endometrium tissues, respectively. The scSpaMet analysis revealed cell type-dependent metabolite profiles and local metabolite competition of neighboring single cells in human tissues. Deep learning-based joint embedding revealed unique metabolite states within cell types. Trajectory inference showed metabolic patterns along cell differentiation paths. Here we show scSpaMet’s ability to quantify and visualize the cell-type specific and spatially resolved metabolic-protein mapping as an emerging tool for systems-level understanding of tissue biology.

Suggested Citation

  • Thomas Hu & Mayar Allam & Shuangyi Cai & Walter Henderson & Brian Yueh & Aybuke Garipcan & Anton V. Ievlev & Maryam Afkarian & Semir Beyaz & Ahmet F. Coskun, 2023. "Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43917-5
    DOI: 10.1038/s41467-023-43917-5
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    References listed on IDEAS

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    1. Alex Baranski & Idan Milo & Shirley Greenbaum & John-Paul Oliveria & Dunja Mrdjen & Michael Angelo & Leeat Keren, 2021. "MAUI (MBI Analysis User Interface)—An image processing pipeline for Multiplexed Mass Based Imaging," PLOS Computational Biology, Public Library of Science, vol. 17(4), pages 1-16, April.
    2. Lucas Seninge & Ioannis Anastopoulos & Hongxu Ding & Joshua Stuart, 2021. "VEGA is an interpretable generative model for inferring biological network activity in single-cell transcriptomics," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    3. Alexander D. Gitlin & Ziv Shulman & Michel C. Nussenzweig, 2014. "Clonal selection in the germinal centre by regulated proliferation and hypermutation," Nature, Nature, vol. 509(7502), pages 637-640, May.
    4. Duc Tran & Hung Nguyen & Bang Tran & Carlo La Vecchia & Hung N. Luu & Tin Nguyen, 2021. "Fast and precise single-cell data analysis using a hierarchical autoencoder," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Hartland W. Jackson & Jana R. Fischer & Vito R. T. Zanotelli & H. Raza Ali & Robert Mechera & Savas D. Soysal & Holger Moch & Simone Muenst & Zsuzsanna Varga & Walter P. Weber & Bernd Bodenmiller, 2020. "The single-cell pathology landscape of breast cancer," Nature, Nature, vol. 578(7796), pages 615-620, February.
    6. Tanja A. Schwickert & Randall L. Lindquist & Guy Shakhar & Geulah Livshits & Dimitris Skokos & Marie H. Kosco-Vilbois & Michael L. Dustin & Michel C. Nussenzweig, 2007. "In vivo imaging of germinal centres reveals a dynamic open structure," Nature, Nature, vol. 446(7131), pages 83-87, March.
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