A lipid atlas of the human kidney.

Journal: Science advances
Published Date: Jun 11, 2025

Abstract

Tissue atlases provide foundational knowledge on the cellular organization and molecular distributions across molecular classes and spatial scales. Here, we construct a comprehensive spatiomolecular lipid atlas of the human kidney from 29 donor tissues using integrated multimodal molecular imaging. Our approach leverages high-spatial-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry for untargeted lipid mapping, stained microscopy for histopathological assessment, and tissue segmentation using autofluorescence microscopy. With a combination of unsupervised, supervised, and interpretable machine learning, the atlas provides multivariate lipid profiles of specific multicellular functional tissue units (FTUs) of the nephron, including the glomerulus, proximal tubules, thick ascending limb, distal tubules, and collecting ducts. In total, the atlas consists of tens of thousands of FTUs and millions of mass spectrometry measurements. Detailed patient, clinical, and histopathologic information allowed molecular data to be mined on the basis of these features. As examples, we highlight the discovery of how lipid profiles are altered with sex and differences in body mass index.

Authors

  • Melissa A Farrow
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Léonore E M Tideman
    Delft Center for Systems and Control, Delft University of Technology, 2628 CD Delft, Netherlands.
  • Elizabeth K Neumann
    Department of Chemistry, University of California Davis, Davis, CA, USA.
  • Lukasz G Migas
    Delft Center for Systems and Control, Delft University of Technology, Delft, Netherlands.
  • Nathan Heath Patterson
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN, USA.
  • Madeline E Colley
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Jamie L Allen
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Ellie L Pingry
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Martin Dufresne
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Haichun Yang
    Vanderbilt University Medical Center, Nashville TN 37232, USA.
  • Maya Brewer
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Emilio S Rivera
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Carrie E Romer
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Katerina Djambazova
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Kavya Sharman
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Angela R S Kruse
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Danielle B Gutierrez
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Raymond C Harris
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Agnes B Fogo
    Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Mark P de Caestecker
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Richard M Caprioli
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN.
  • Raf Van de Plas
    Delft Center for Systems and Control, Delft University of Technology - TU Delft, Delft, The Netherlands.
  • Jeffrey M Spraggins
    Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA.

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