{
  "abstract": "Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition impacting over 30% population, yet the dynamic changes in macrophage composition from steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH) remain unclear. Here, by integrating single-nucleus transcriptomics, spatial multi-omics and proteomics on human samples, we delineate the evolving landscape of hepatic macrophages across the MASLD spectrum. Our analysis reveals a progressive depletion of Kupffer cells accompanied by the emergence of diverse, phenotypically distinct macrophage subsets. Spatial multi-omics further demonstrates that disease progression toward MASH is marked by an accumulation of antigen-presenting, phagocytic GPNMB+ macrophages, supported by IL32-producing hepatocytes. These macrophages showed an adaptive metabolic and pro-inflammatory phenotype that is tightly regulated by both spatial context and disease stage. Identified macrophage markers enable patient stratification by disease activity and its stage across independent clinical cohorts. Our study sheds light on the diversity of macrophage identities and metabolic-adaptive phenotypes during the progression of MASLD. This study uses multi-omics approaches to dissect the roles of macrophage populations in the progression of metabolic dysfunction-associated steatohepatitis. GPNMB+ macrophages accumulate in the portal tract in advanced disease and may have antigen-presenting capabilities.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium",
    "KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium",
    "Laboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium",
    "Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium",
    "Bruker Spatial Biology, Seattle, WA, USA",
    "Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden",
    "Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium",
    "Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK",
    "Department of Abdominal Surgery, UZ Leuven, Leuven, Belgium",
    "Center for Regenerative Therapies Dresden (CRTD), TUD Dresden University of Technology, Dresden, Germany",
    "Department of Medicine 1, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Dresden, Germany",
    "Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany",
    "Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany",
    "Clinica Medica 'C. Frugoni' and Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Bari, Italy",
    "Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, UK",
    "Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge NIHR Biomedical Research Centre, Cambridge, UK",
    "Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden",
    "Hepatology Department, Angers University Hospital, Angers, France",
    "Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy",
    "Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Sorbonne University, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France",
    "Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium",
    "VIB Center for Cancer Biology, Leuven, Belgium",
    "Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany",
    "Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium",
    "Translational Research in Inflammation and Immunology (TWI2N), Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium",
    "Institute of Medical Microbiology, Medical centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany",
    "Department of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece",
    "Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK. quentin.anstee@newcastle.ac.uk",
    "Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. quentin.anstee@newcastle.ac.uk",
    "Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium. schalk.vandermerwe@uzleuven.be",
    "Laboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium. schalk.vandermerwe@uzleuven.be",
    "Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium. olivier.govaere@kuleuven.be",
    "KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium. olivier.govaere@kuleuven.be",
    "Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. olivier.govaere@kuleuven.be"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 48,
  "authors": [
    {
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        0,
        1,
        2,
        3
      ],
      "name": "Markus Boesch",
      "orcid": "0000-0003-2483-9583"
    },
    {
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        0
      ],
      "name": "Seray Anak"
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      "name": "Dania El Abyad",
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      "name": "Tessa Ostyn",
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      "name": "Asier Antoranz",
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      "name": "Trieu My Van"
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      "name": "Daniel Newhouse"
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      "name": "Caitlyn Myers",
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      "name": "Lukas Van Melkebeke",
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      "name": "Jeremy M. Palmer",
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      "name": "Najmeh Saffarzadeh"
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      "name": "Jonathan Sai‐Hong Chui",
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      "name": "Rita Feio‐Azevedo",
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      "name": "Lena Smets",
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      "name": "Gautam Shankar"
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      "name": "Nikolina Dubroja"
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      "name": "Paula Longás Calvo"
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      "name": "Thierry Voet",
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      "name": "James A. Clark",
      "orcid": "0000-0002-7888-5684"
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      "name": "Simon Cockell",
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      "name": "Matthias Lannoo",
      "orcid": "0000-0001-7815-1157"
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        8
      ],
      "name": "Ellen Deleus",
      "orcid": "0000-0002-8496-7723"
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    {
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        8
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      "name": "Joris Jaekers",
      "orcid": "0000-0001-5101-4574"
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    {
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        8
      ],
      "name": "Halit Topal",
      "orcid": "0000-0002-5869-6296"
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    {
      "affs": [
        8
      ],
      "name": "Baki Topal",
      "orcid": "0000-0002-2687-7535"
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    {
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        9,
        10,
        11,
        12
      ],
      "name": "Kai Markus Schneider",
      "orcid": "0000-0002-0047-3794"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Michele Vacca",
      "orcid": "0000-0002-1973-224X"
    },
    {
      "affs": [
        15
      ],
      "name": "Michael Allison",
      "orcid": "0000-0003-3677-3294"
    },
    {
      "affs": [
        16
      ],
      "name": "Mattias Ekstedt",
      "orcid": "0000-0002-5590-8601"
    },
    {
      "affs": [
        17
      ],
      "name": "Jérôme Boursier",
      "orcid": "0000-0002-7282-1436"
    },
    {
      "affs": [
        18
      ],
      "name": "Elisabetta Bugianesi",
      "orcid": "0000-0002-0502-4381"
    },
    {
      "affs": [
        19
      ],
      "name": "Vlad Ratziu",
      "orcid": "0000-0002-6865-3791"
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        1
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      "name": "Frederik De Smet",
      "orcid": "0000-0002-6669-3335"
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    {
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        20,
        21
      ],
      "name": "Bram Boeckx",
      "orcid": "0000-0002-0296-6680"
    },
    {
      "affs": [
        7
      ],
      "name": "Ann K. Daly",
      "orcid": "0000-0002-7321-0629"
    },
    {
      "affs": [
        22
      ],
      "name": "Jörn Markus Schattenberg",
      "orcid": "0000-0002-4224-4703"
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    {
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        6,
        2
      ],
      "name": "Jef Verbeek",
      "orcid": "0000-0002-1549-8003"
    },
    {
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        0,
        1
      ],
      "name": "Francesca Maria Bosisio",
      "orcid": "0000-0002-8874-2003"
    },
    {
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        20,
        21
      ],
      "name": "Diether Lambrechts",
      "orcid": "0000-0002-3429-302X"
    },
    {
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        0
      ],
      "name": "Tania Roskams",
      "orcid": "0000-0002-2816-1530"
    },
    {
      "affs": [
        12
      ],
      "name": "Carolin V. Schneider",
      "orcid": "0000-0002-6728-9246"
    },
    {
      "affs": [
        23,
        24
      ],
      "name": "Sven Francque",
      "orcid": "0000-0002-7527-4714"
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    {
      "affs": [
        2
      ],
      "name": "Hannelie Korf",
      "orcid": "0000-0003-3540-0138"
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    {
      "affs": [
        25,
        5
      ],
      "name": "Anetta Härtlová",
      "orcid": "0000-0002-8152-4361"
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    {
      "affs": [
        26,
        7
      ],
      "name": "DINA G. TINIAKOS",
      "orcid": "0000-0003-4657-7780"
    },
    {
      "affs": [
        27,
        28
      ],
      "name": "Quentin Mark Anstee",
      "orcid": "0000-0002-9518-0088"
    },
    {
      "affs": [
        29,
        30
      ],
      "name": "S Van der Merwe",
      "orcid": "0000-0002-0452-1183"
    },
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        31,
        32,
        33
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      "name": "Olivier Govaere",
      "orcid": "0000-0002-4426-6930"
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  ],
  "bibtex": "https://research.draconitic.com/paper/63y9s7b3nz5wj.bib",
  "cited_by": 13,
  "doi": "10.1038/s41588-026-02600-3",
  "fulltext_url": null,
  "id": "63y9s7b3nz5wj",
  "issns": [
    "1061-4036",
    "1546-1718"
  ],
  "landing_url": "https://hal.science/hal-05840385v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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    [
      "openalex",
      "2713|Liver Disease Diagnosis and Treatment"
    ],
    [
      "openalex",
      "2721|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7161577121",
  "pdf_url": null,
  "pmcid": "PMC13263141",
  "pmid": "42151416",
  "published": "2026-05-18",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/63y9s7b3nz5wj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "hal-05840385",
      "source": "hal",
      "url": "https://hal.science/hal-05840385v1"
    },
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W7161577121",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41588-026-02600-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Liver Disease Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis",
  "title_text": "Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:16Z",
  "url": "https://research.draconitic.com/paper/63y9s7b3nz5wj",
  "venue": "Nature Genetics",
  "versions": []
}