A lipid atlas of the human kidney
Year: 2025
Type: article
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.
Source: Science Advances
Authors: Melissa A. Farrow, Léonore E.M. Tideman, Elizabeth K. Neumann, Nathan Heath Patterson, Lukasz G. Migas, Madeline E. Colley, Jamie L. Allen, Emilio S. Rivera, Carrie E. Romer, Haichun Yang, Maya Brewer, Ellie Pingry, Martin Dufresne, Katerina Djambazova, Kavya Sharman, Angela R.S. Kruse, Danielle B. Gutierrez, Raymond C. Harris, Agnes B. Fogo, Mark P. de Caestecker, Richard M. Caprioli, Raf Van de Plas, Jeffrey M. Spraggins
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: National Science Foundation, European Commission, ZonMw, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, Horizon 2020 Framework Programme, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Chemical, Bioengineering, Environmental, and Transport Systems, Common Fund
Awards: G1255259016, G1809294206, Vanderbilt University Biomolecular Multimodal Imaging Center for 3-Dimensional Tissue Mapping, G3298167325, G3606619490, G4175096997, G434337789, G4960608113, G5187601199, Human Brain Project Specific Grant Agreement 2, Tennessee Valley Cooperative Human Tissue Network, G6607577419, G6754083667, Advanced Morphological Reconstruction of Human Brain Tissue by Multimodal Fusion of Multiscale Optical Imaging Technologies, MRI: Development of a next-generation MALDI ion mobility mass spectrometry platform for molecular imaging and training, G7474264879, G8334248497, G9000091806
OpenAlex ID: W4411193869