ArticleNature genetics2026
Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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2 citing papers in PubMed.
- A human single-cell atlas identifies OLR1Nature genetics · 2026Article
- Dysfunctional macrophages along the gut-liver axis: a driver of infection in cirrhosis.Frontiers in immunology · 2026Review
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Authors and funding
48 authors.
Markus BoeschLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-2483-9583
Seray Anak *Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Dania El Abyad *Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID http://orcid.org/0009-0004-2083-0236
Tessa OstynDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Asier AntoranzDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-7284-610X
Trieu My VanBruker Spatial Biology, Seattle, WA, USA.
Daniel NewhouseBruker Spatial Biology, Seattle, WA, USA.
Caitlyn MyersWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Lukas Van MelkebekeLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Jeremy PalmerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Najmeh SaffarzadehWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Jonathan Sai-Hong ChuiDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-8319-5947
Rita Feio-AzevedoLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Lena SmetsLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Gautam ShankarDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Nikolina Dubroja LakićDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Paula Longás CalvoKU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.
Thierry VoetKU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-1204-9963
James ClarkTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-7155-0961
Simon CockellTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-6831-9806
Matthias LannooDepartment of Abdominal Surgery, UZ Leuven, Leuven, Belgium.
Ellen DeleusDepartment of Abdominal Surgery, UZ Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-8496-7723
Joris JaekersDepartment of Abdominal Surgery, UZ Leuven, Leuven, Belgium.
Halit TopalDepartment of Abdominal Surgery, UZ Leuven, Leuven, Belgium.
Baki TopalDepartment of Abdominal Surgery, UZ Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-2687-7535
Kai Markus SchneiderMedical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Michele VaccaRoger 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.ORCID http://orcid.org/0000-0002-1973-224X
Michael AllisonCambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge NIHR Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0003-3677-3294
Mattias EkstedtDepartment of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.ORCID http://orcid.org/0000-0002-5590-8601
Jerome BoursierHepatology Department, Angers University Hospital, Angers, France.
Elisabetta BugianesiDepartment of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Vlad RatziuAssistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Sorbonne University, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
Frederik De SmetDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-6669-3335
Bram BoeckxLaboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-0296-6680
Ann K DalyTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-7321-0629
Jörn M SchattenbergDepartment of Internal Medicine II, Saarland University Medical Center, Homburg, Germany.ORCID http://orcid.org/0000-0002-4224-4703
Jef VerbeekLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Francesca BosisioDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-8874-2003
Diether LambrechtsLaboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-3429-302X
Tania RoskamsDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Carolin V SchneiderMedical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Sven FrancqueDepartment of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
Hannelie KorfLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Anetta HärtlovaWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-8152-4361
Dina TiniakosTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-4657-7780
Quentin M AnsteeTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. quentin.anstee@newcastle.ac.uk.ORCID http://orcid.org/0000-0002-9518-0088
Schalk van der MerweLaboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium. schalk.vandermerwe@uzleuven.be.ORCID http://orcid.org/0000-0002-9891-2686
Olivier GovaereDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium. olivier.govaere@kuleuven.be.ORCID http://orcid.org/0000-0002-4426-6930
Funding
Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 12ATN24NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G032324NInnovative Medicines Initiative (IMI) 777377
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
Indexed as
Fatty LiverMacrophagesNon-alcoholic Fatty Liver DiseaseAnimalsDisease ProgressionGene Expression ProfilingHepatocytesHumansKupffer CellsLiverMembrane GlycoproteinsMultiomicsProteomicsTranscriptomeGPNMB protein, humanMembrane Glycoproteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.