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Spatial patterns of hepatocyte glucose flux revealed by stable isotope tracing and multi-scale microscopy

Author

Listed:
  • Aliyah Habashy

    (Vanderbilt University)

  • Christopher Acree

    (Vanderbilt University)

  • Keun-Young Kim

    (University of California San Diego, School of Medicine)

  • Ali Zahraei

    (Vanderbilt University
    Vanderbilt University School of Medicine)

  • Martin Dufresne

    (Vanderbilt University
    Vanderbilt University School of Medicine)

  • Sebastien Phan

    (University of California San Diego, School of Medicine)

  • Melanie Cutler

    (Vanderbilt University)

  • Emilee Patterson

    (Vanderbilt University)

  • Alexandra G. Mulligan

    (Vanderbilt University)

  • Kristopher Burkewitz

    (Vanderbilt University)

  • Charles Robert Flynn

    (Vanderbilt University Medical Center)

  • Louise Lantier

    (Vanderbilt University)

  • Thomas Deerinck

    (University of California San Diego, School of Medicine)

  • Owen P. McGuinness

    (Vanderbilt University)

  • Jeffrey M. Spraggins

    (Vanderbilt University
    Vanderbilt University School of Medicine
    Vanderbilt University
    Vanderbilt University)

  • Mark H. Ellisman

    (University of California San Diego, School of Medicine)

  • Rafael Arrojo e Drigo

    (Vanderbilt University
    Vanderbilt University
    Vanderbilt University Medical Center)

Abstract

Metabolic homeostasis requires engagement of catabolic and anabolic pathways consuming nutrients that generate and consume energy and biomass. Our current understanding of cell homeostasis and metabolism, including how cells utilize nutrients, comes largely from tissue and cell models analyzed after fractionation, and that fail to reveal the spatial characteristics of cell metabolism, and how these aspects relate to the location of cells and organelles within tissue microenvironments. Here we show the application of multi-scale microscopy, machine learning-based image segmentation, and spatial analysis tools to quantitatively map the fate of nutrient-derived 13C atoms across spatiotemporal scales. This approach reveals the cellular and organellar features underlying the spatial pattern of glucose 13C flux in hepatocytes in situ, including the timeline of mitochondria-ER contact dynamics in response to changes in blood glucose levels, and the discovery of the ultrastructural relationship between glycogenesis and lipid droplets.

Suggested Citation

  • Aliyah Habashy & Christopher Acree & Keun-Young Kim & Ali Zahraei & Martin Dufresne & Sebastien Phan & Melanie Cutler & Emilee Patterson & Alexandra G. Mulligan & Kristopher Burkewitz & Charles Robert, 2025. "Spatial patterns of hepatocyte glucose flux revealed by stable isotope tracing and multi-scale microscopy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60994-w
    DOI: 10.1038/s41467-025-60994-w
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