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Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution

Author

Listed:
  • Marija Veličković

    (Pacific Northwest National Laboratory)

  • Leena Kadam

    (Oregon Health & Science University)

  • Joonhoon Kim

    (Pacific Northwest National Laboratory)

  • Kevin J. Zemaitis

    (Pacific Northwest National Laboratory)

  • Dušan Veličković

    (Pacific Northwest National Laboratory)

  • Yuqian Gao

    (Pacific Northwest National Laboratory)

  • Ruonan Wu

    (Pacific Northwest National Laboratory)

  • Thomas L. Fillmore

    (Pacific Northwest National Laboratory)

  • Daniel Orton

    (Pacific Northwest National Laboratory)

  • Sarah M. Williams

    (Pacific Northwest National Laboratory)

  • Matthew E. Monroe

    (Pacific Northwest National Laboratory)

  • Ronald J. Moore

    (Pacific Northwest National Laboratory)

  • Paul D. Piehowski

    (Pacific Northwest National Laboratory)

  • Lisa M. Bramer

    (Pacific Northwest National Laboratory)

  • Leslie Myatt

    (Oregon Health & Science University)

  • Kristin E. Burnum-Johnson

    (Pacific Northwest National Laboratory)

Abstract

The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems-level understanding of molecular changes underlying the mechanisms leading to the histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we advance our metabolome-informed proteome imaging (MIPI) workflow to include lipidomic imaging, while also expanding the molecular coverage of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). The improved MIPI workflow advances biomedical investigations by leveraging state-of-the-art molecular imaging technologies. Lipidome imaging identifies molecular differences between two morphologically distinct compartments of a placental villous functional unit, syncytiotrophoblast (STB) and villous core. Next, our advanced metabolome imaging maps villous functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villous compartments. Complementary proteome imaging on these villous functional units reveals a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and villous core compartments. Integration across our advanced MIPI imaging modalities enables the reconstruction of active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villous compartments with micrometer-scale resolution.

Suggested Citation

  • Marija Veličković & Leena Kadam & Joonhoon Kim & Kevin J. Zemaitis & Dušan Veličković & Yuqian Gao & Ruonan Wu & Thomas L. Fillmore & Daniel Orton & Sarah M. Williams & Matthew E. Monroe & Ronald J. M, 2025. "Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57107-y
    DOI: 10.1038/s41467-025-57107-y
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    References listed on IDEAS

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    1. Shirley Greenbaum & Inna Averbukh & Erin Soon & Gabrielle Rizzuto & Alex Baranski & Noah F. Greenwald & Adam Kagel & Marc Bosse & Eleni G. Jaswa & Zumana Khair & Shirley Kwok & Shiri Warshawsky & Hade, 2023. "A spatially resolved timeline of the human maternal–fetal interface," Nature, Nature, vol. 619(7970), pages 595-605, July.
    2. Paul D. Piehowski & Ying Zhu & Lisa M. Bramer & Kelly G. Stratton & Rui Zhao & Daniel J. Orton & Ronald J. Moore & Jia Yuan & Hugh D. Mitchell & Yuqian Gao & Bobbie-Jo M. Webb-Robertson & Sudhansu K. , 2020. "Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Roser Vento-Tormo & Mirjana Efremova & Rachel A. Botting & Margherita Y. Turco & Miquel Vento-Tormo & Kerstin B. Meyer & Jong-Eun Park & Emily Stephenson & Krzysztof Polański & Angela Goncalves & Lucy, 2018. "Single-cell reconstruction of the early maternal–fetal interface in humans," Nature, Nature, vol. 563(7731), pages 347-353, November.
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