{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T03:49:59Z","timestamp":1794541799653,"version":"4.9.1"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G032324N"],"award-info":[{"award-number":["G032324N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["12ATN24N"],"award-info":[{"award-number":["12ATN24N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["777377"],"award-info":[{"award-number":["777377"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1038\/s41588-026-02600-3","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:01:20Z","timestamp":1779094880000},"page":"1295-1307","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis"],"prefix":"10.1038","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2483-9583","authenticated-orcid":false,"given":"Markus","family":"Boesch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seray","family":"Anak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2083-0236","authenticated-orcid":false,"given":"Dania","family":"El Abyad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Ostyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-610X","authenticated-orcid":false,"given":"Asier","family":"Antoranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trieu","family":"My Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Newhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Van Melkebeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmeh","family":"Saffarzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-5947","authenticated-orcid":false,"given":"Jonathan Sai-Hong","family":"Chui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Feio-Azevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Smets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolina","family":"Dubroja Laki\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Long\u00e1s","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1204-9963","authenticated-orcid":false,"given":"Thierry","family":"Voet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7155-0961","authenticated-orcid":false,"given":"James","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-9806","authenticated-orcid":false,"given":"Simon","family":"Cockell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Lannoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8496-7723","authenticated-orcid":false,"given":"Ellen","family":"Deleus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Jaekers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halit","family":"Topal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-7535","authenticated-orcid":false,"given":"Baki","family":"Topal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Markus","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-224X","authenticated-orcid":false,"given":"Michele","family":"Vacca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-3294","authenticated-orcid":false,"given":"Michael","family":"Allison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5590-8601","authenticated-orcid":false,"given":"Mattias","family":"Ekstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Boursier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Bugianesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Ratziu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6669-3335","authenticated-orcid":false,"given":"Frederik","family":"De Smet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0296-6680","authenticated-orcid":false,"given":"Bram","family":"Boeckx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-0629","authenticated-orcid":false,"given":"Ann K.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-4703","authenticated-orcid":false,"given":"J\u00f6rn M.","family":"Schattenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jef","family":"Verbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-2003","authenticated-orcid":false,"given":"Francesca","family":"Bosisio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-302X","authenticated-orcid":false,"given":"Diether","family":"Lambrechts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Roskams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin V.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Francque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannelie","family":"Korf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8152-4361","authenticated-orcid":false,"given":"Anetta","family":"H\u00e4rtlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4657-7780","authenticated-orcid":false,"given":"Dina","family":"Tiniakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-0088","authenticated-orcid":false,"given":"Quentin M.","family":"Anstee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-2686","authenticated-orcid":false,"given":"Schalk","family":"van der Merwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-6930","authenticated-orcid":false,"given":"Olivier","family":"Govaere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"2600_CR1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","volume":"16","author":"QM Anstee","year":"2019","unstructured":"Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O. & Heikenwalder, M. From NASH to HCC: current concepts and future challenges. Nat. Rev. Gastroenterol. Hepatol. 16, 411\u2013428 (2019).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2600_CR2","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41575-023-00807-x","volume":"20","author":"L Hammerich","year":"2023","unstructured":"Hammerich, L. & Tacke, F. Hepatic inflammatory responses in liver fibrosis. Nat. Rev. Gastroenterol. Hepatol. 20, 633\u2013646 (2023).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2600_CR3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41574-022-00675-6","volume":"18","author":"E Barreby","year":"2022","unstructured":"Barreby, E., Chen, P. & Aouadi, M. Macrophage functional diversity in NAFLD\u2014more than inflammation. Nat. Rev. Endocrinol. 18, 461\u2013472 (2022).","journal-title":"Nat. Rev. Endocrinol."},{"key":"2600_CR4","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","volume":"79","author":"ME Rinella","year":"2023","unstructured":"Rinella, M. E. et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 79, 1542\u20131556 (2023).","journal-title":"J. Hepatol."},{"key":"2600_CR5","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2023.04.036","volume":"79","author":"VW Wong","year":"2023","unstructured":"Wong, V. W., Ekstedt, M., Wong, G. L. & Hagstrom, H. Changing epidemiology, global trends and implications for outcomes of NAFLD. J. Hepatol. 79, 842\u2013852 (2023).","journal-title":"J. Hepatol."},{"key":"2600_CR6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s42255-023-00775-1","volume":"5","author":"O Govaere","year":"2023","unstructured":"Govaere, O. et al. A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures. Nat. Metab. 5, 572\u2013578 (2023).","journal-title":"Nat. Metab."},{"key":"2600_CR7","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.immuni.2020.06.003","volume":"53","author":"S Tran","year":"2020","unstructured":"Tran, S. et al. Impaired Kupffer cell self-renewal alters the liver response to lipid overload during non-alcoholic steatohepatitis. Immunity 53, 627\u2013640 (2020).","journal-title":"Immunity"},{"key":"2600_CR8","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.immuni.2020.08.004","volume":"53","author":"A Remmerie","year":"2020","unstructured":"Remmerie, A. et al. Osteopontin expression identifies a subset of recruited macrophages distinct from Kupffer cells in the fatty liver. Immunity 53, 641\u2013657 (2020).","journal-title":"Immunity"},{"key":"2600_CR9","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.cell.2019.05.054","volume":"178","author":"DA Jaitin","year":"2019","unstructured":"Jaitin, D. A. et al. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178, 686\u2013698 (2019).","journal-title":"Cell"},{"key":"2600_CR10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1053\/j.gastro.2023.03.228","volume":"165","author":"H Han","year":"2023","unstructured":"Han, H. et al. Macrophage-derived osteopontin (SPP1) protects from nonalcoholic steatohepatitis. Gastroenterology 165, 201\u2013217 (2023).","journal-title":"Gastroenterology"},{"key":"2600_CR11","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.jhep.2022.06.004","volume":"77","author":"T Hendrikx","year":"2022","unstructured":"Hendrikx, T. et al. Soluble TREM2 levels reflect the recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH. J. Hepatol. 77, 1373\u20131385 (2022).","journal-title":"J. Hepatol."},{"key":"2600_CR12","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2405746121","volume":"121","author":"S Ganguly","year":"2024","unstructured":"Ganguly, S. et al. Lipid-associated macrophages\u2019 promotion of fibrosis resolution during MASH regression requires TREM2. Proc. Natl Acad. Sci. USA 121, e2405746121 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2600_CR13","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","volume":"575","author":"P Ramachandran","year":"2019","unstructured":"Ramachandran, P. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512\u2013518 (2019).","journal-title":"Nature"},{"key":"2600_CR14","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.add8945","volume":"8","author":"T Fabre","year":"2023","unstructured":"Fabre, T. et al. Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation. Sci. Immunol. 8, eadd8945 (2023).","journal-title":"Sci. Immunol."},{"key":"2600_CR15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cell.2021.12.018","volume":"185","author":"M Guilliams","year":"2022","unstructured":"Guilliams, M. et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell 185, 379\u2013396 (2022).","journal-title":"Cell"},{"key":"2600_CR16","volume":"6","author":"FF De Ponti","year":"2024","unstructured":"De Ponti, F. F., Liu, Z. & Scott, C. L. Understanding the complex macrophage landscape in MASLD. JHEP Rep. 6, 101196 (2024).","journal-title":"JHEP Rep."},{"key":"2600_CR17","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1038\/s42255-022-00700-y","volume":"4","author":"S Gallage","year":"2022","unstructured":"Gallage, S. et al. A researcher\u2019s guide to preclinical mouse NASH models. Nat. Metab. 4, 1632\u20131649 (2022).","journal-title":"Nat. Metab."},{"key":"2600_CR18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.jhep.2023.04.037","volume":"79","author":"E Kotsiliti","year":"2023","unstructured":"Kotsiliti, E. et al. Intestinal B cells license metabolic T-cell activation in NASH microbiota\/antigen-independently and contribute to fibrosis by IgA-FcR signalling. J. Hepatol. 79, 296\u2013313 (2023).","journal-title":"J. Hepatol."},{"key":"2600_CR19","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/HEP.0000000000000270","volume":"78","author":"A Guillot","year":"2023","unstructured":"Guillot, A. et al. Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression. Hepatology 78, 150\u2013166 (2023).","journal-title":"Hepatology"},{"key":"2600_CR20","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/hep.22724","volume":"49","author":"EM Brunt","year":"2009","unstructured":"Brunt, E. M. et al. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 49, 809\u2013820 (2009).","journal-title":"Hepatology"},{"key":"2600_CR21","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","volume":"149","author":"P Angulo","year":"2015","unstructured":"Angulo, P. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389\u2013397 (2015).","journal-title":"Gastroenterology"},{"key":"2600_CR22","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aba4448","volume":"12","author":"O Govaere","year":"2020","unstructured":"Govaere, O. et al. Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis. Sci. Transl. Med. 12, eaba4448 (2020).","journal-title":"Sci. Transl. Med."},{"key":"2600_CR23","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313\u20131321 (2005).","journal-title":"Hepatology"},{"key":"2600_CR24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41586-024-07465-2","volume":"630","author":"C Gribben","year":"2024","unstructured":"Gribben, C. et al. Acquisition of epithelial plasticity in human chronic liver disease. Nature 630, 166\u2013173 (2024).","journal-title":"Nature"},{"key":"2600_CR25","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/s41587-022-01483-z","volume":"40","author":"S He","year":"2022","unstructured":"He, S. et al. High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat. Biotechnol. 40, 1794\u20131806 (2022).","journal-title":"Nat. Biotechnol."},{"key":"2600_CR26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1369\/0022155417719419","volume":"65","author":"MM Bolognesi","year":"2017","unstructured":"Bolognesi, M. M. et al. Multiplex staining by sequential immunostaining and antibody removal on routine tissue sections. J. Histochem. Cytochem. 65, 431\u2013444 (2017).","journal-title":"J. Histochem. Cytochem."},{"key":"2600_CR27","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1158\/0008-5472.CAN-22-0363","volume":"82","author":"A Antoranz","year":"2022","unstructured":"Antoranz, A. et al. Mapping the immune landscape in metastatic melanoma reveals localized cell-cell interactions that predict immunotherapy response. Cancer Res. 82, 3275\u20133290 (2022).","journal-title":"Cancer Res."},{"key":"2600_CR28","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1136\/gutjnl-2019-319226","volume":"69","author":"GA Baselli","year":"2020","unstructured":"Baselli, G. A. et al. Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker. Gut 69, 1855\u20131866 (2020).","journal-title":"Gut"},{"key":"2600_CR29","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.jhep.2021.12.012","volume":"76","author":"O Govaere","year":"2022","unstructured":"Govaere, O. et al. Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease. J. Hepatol. 76, 1001\u20131012 (2022).","journal-title":"J. Hepatol."},{"key":"2600_CR30","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun, B. B. et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622, 329\u2013338 (2023).","journal-title":"Nature"},{"key":"2600_CR31","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman, A. M. et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat. Biotechnol. 37, 773\u2013782 (2019).","journal-title":"Nat. Biotechnol."},{"key":"2600_CR32","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.jacl.2016.02.015","volume":"10","author":"P Pingitore","year":"2016","unstructured":"Pingitore, P. et al. Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia. J. Clin. Lipidol. 10, 816\u2013823 (2016).","journal-title":"J. Clin. Lipidol."},{"key":"2600_CR33","doi-asserted-by":"crossref","first-page":"26293","DOI":"10.1074\/jbc.M002423200","volume":"275","author":"VR Babaev","year":"2000","unstructured":"Babaev, V. R., Patel, M. B., Semenkovich, C. F., Fazio, S. & Linton, M. F. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. J. Biol. Chem. 275, 26293\u201326299 (2000).","journal-title":"J. Biol. Chem."},{"key":"2600_CR34","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1194\/jlr.M035568","volume":"54","author":"M Takahashi","year":"2013","unstructured":"Takahashi, M. et al. Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity. J. Lipid Res. 54, 1124\u20131134 (2013).","journal-title":"J. Lipid Res."},{"key":"2600_CR35","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1161\/ATVBAHA.123.318974","volume":"43","author":"J Tan","year":"2023","unstructured":"Tan, J. et al. Single-cell transcriptomics reveals crucial cell subsets and functional heterogeneity associated with carotid atherosclerosis and cerebrovascular events. Arterioscler. Thromb. Vasc. Biol. 43, 2312\u20132332 (2023).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2600_CR36","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1073\/pnas.0712381105","volume":"105","author":"MG Netea","year":"2008","unstructured":"Netea, M. G. et al. Interleukin-32 induces the differentiation of monocytes into macrophage-like cells. Proc. Natl Acad. Sci. USA 105, 3515\u20133520 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2600_CR37","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s12276-025-01408-1","volume":"57","author":"JS Park","year":"2025","unstructured":"Park, J. S. et al. A1AT dysregulation of metabolically stressed hepatocytes by Kupffer cells drives MASH and fibrosis. Exp. Mol. Med. 57, 450\u2013465 (2025).","journal-title":"Exp. Mol. Med."},{"key":"2600_CR38","volume":"5","author":"K Sasidharan","year":"2024","unstructured":"Sasidharan, K. et al. IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids. Cell Rep. Med. 5, 101352 (2024).","journal-title":"Cell Rep. Med."},{"key":"2600_CR39","first-page":"E3186","volume":"109","author":"P Ramachandran","year":"2012","unstructured":"Ramachandran, P. et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc. Natl Acad. Sci. USA 109, E3186\u2013E3195 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2600_CR40","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1038\/s41388-022-02443-2","volume":"41","author":"AM Lazaratos","year":"2022","unstructured":"Lazaratos, A. M., Annis, M. G. & Siegel, P. M. GPNMB: a potent inducer of immunosuppression in cancer. Oncogene 41, 4573\u20134590 (2022).","journal-title":"Oncogene"},{"key":"2600_CR41","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.2337\/db13-1720","volume":"63","author":"TL Gabriel","year":"2014","unstructured":"Gabriel, T. L. et al. Lysosomal stress in obese adipose tissue macrophages contributes to MITF-dependent Gpnmb induction. Diabetes 63, 3310\u20133323 (2014).","journal-title":"Diabetes"},{"key":"2600_CR42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jhep.2023.10.039","volume":"80","author":"M Boesch","year":"2024","unstructured":"Boesch, M. et al. Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASH. J. Hepatol. 80, 397\u2013408 (2024).","journal-title":"J. Hepatol."},{"key":"2600_CR43","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41586-024-07372-6","volume":"629","author":"Y Miyamoto","year":"2024","unstructured":"Miyamoto, Y. et al. Periportal macrophages protect against commensal-driven liver inflammation. Nature 629, 901\u2013909 (2024).","journal-title":"Nature"},{"key":"2600_CR44","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s42255-019-0065-4","volume":"1","author":"XM Gong","year":"2019","unstructured":"Gong, X. M. et al. Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance. Nat. Metab. 1, 570\u2013583 (2019).","journal-title":"Nat. Metab."},{"key":"2600_CR45","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/s41586-020-2499-y","volume":"583","author":"N Schaum","year":"2020","unstructured":"Schaum, N. et al. Ageing hallmarks exhibit organ-specific temporal signatures. Nature 583, 596\u2013602 (2020).","journal-title":"Nature"},{"key":"2600_CR46","doi-asserted-by":"crossref","DOI":"10.1016\/j.cct.2020.106175","volume":"98","author":"T Hardy","year":"2020","unstructured":"Hardy, T. et al. The European NAFLD registry: a real-world longitudinal cohort study of nonalcoholic fatty liver disease. Contemp. Clin. Trials 98, 106175 (2020).","journal-title":"Contemp. Clin. Trials"},{"key":"2600_CR47","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giaa151","volume":"9","author":"MD Young","year":"2020","unstructured":"Young, M. D. & Behjati, S. SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data. Gigascience 9, giaa151 (2020).","journal-title":"Gigascience"},{"key":"2600_CR48","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587 (2021).","journal-title":"Cell"},{"key":"2600_CR49","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.73600.1","volume":"10","author":"PL Germain","year":"2021","unstructured":"Germain, P. L., Lun, A., Garcia Meixide, C., Macnair, W. & Robinson, M. D. Doublet identification in single-cell sequencing data using scDblFinder. F1000Res 10, 979 (2021).","journal-title":"F1000Res"},{"key":"2600_CR50","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-06318-7","volume":"9","author":"SA MacParland","year":"2018","unstructured":"MacParland, S. A. et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9, 4383 (2018).","journal-title":"Nat. Commun."},{"key":"2600_CR51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41587-021-01033-z","volume":"40","author":"E Dann","year":"2022","unstructured":"Dann, E., Henderson, N. C., Teichmann, S. A., Morgan, M. D. & Marioni, J. C. Differential abundance testing on single-cell data using k-nearest neighbor graphs. Nat. Biotechnol. 40, 245\u2013253 (2022).","journal-title":"Nat. Biotechnol."},{"key":"2600_CR52","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","volume":"15","author":"M Efremova","year":"2020","unstructured":"Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell\u2013cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 15, 1484\u20131506 (2020).","journal-title":"Nat. Protoc."},{"key":"2600_CR53","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-28020-5","volume":"13","author":"P Danaher","year":"2022","unstructured":"Danaher, P. et al. Advances in mixed cell deconvolution enable quantification of cell types in spatial transcriptomic data. Nat. Commun. 13, 385 (2022).","journal-title":"Nat. Commun."},{"key":"2600_CR54","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"2600_CR55","doi-asserted-by":"publisher","unstructured":"Govaere, O. GeoMx Human Whole Transcriptome Atlas profiling on at-risk MASH F3 patients [data set]. Zenodo https:\/\/doi.org\/10.5281\/zenodo.18153344 (2026).","DOI":"10.5281\/zenodo.18153344"},{"key":"2600_CR56","doi-asserted-by":"publisher","unstructured":"B\u00f6sch, M., Anak, S., Ostyn, T., El Abyad, D. & Govaere, O. Metabolic dysfunction-associated steatohepatitis (MASH) GeoMx and COMET dataset (version V1) [dataset]. KU Leuven RDR https:\/\/doi.org\/10.48804\/ERGUWX (2025).","DOI":"10.48804\/ERGUWX"},{"key":"2600_CR57","doi-asserted-by":"publisher","unstructured":"Govaere, O. MILAN multiplex proteomics stainings of human MASLD biopsies: digital reconstructions and overlay images. figshare. figure https:\/\/doi.org\/10.6084\/m9.figshare.31986669.v1 (2026).","DOI":"10.6084\/m9.figshare.31986669.v1"},{"key":"2600_CR58","doi-asserted-by":"publisher","unstructured":"Govaere, O. DAB images of liver biopsies with GPNMB staining. figshare https:\/\/doi.org\/10.6084\/m9.figshare.28881296.v1 (2025).","DOI":"10.6084\/m9.figshare.28881296.v1"},{"key":"2600_CR59","doi-asserted-by":"publisher","unstructured":"Govaere, O. DAB stainings of human liver samples with the markers used in immunofluorescence multiplexing. figshare https:\/\/doi.org\/10.6084\/m9.figshare.28881638.v2 (2025).","DOI":"10.6084\/m9.figshare.28881638.v2"},{"key":"2600_CR60","doi-asserted-by":"publisher","unstructured":"Boesch, M. Integrated multi-omics of metabolic dysfunction-associated steatohepatitis. Zenodo https:\/\/doi.org\/10.5281\/zenodo.17980902 (2025).","DOI":"10.5281\/zenodo.17980902"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02600-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02600-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02600-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:40:19Z","timestamp":1781271619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02600-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":60,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2600"],"URL":"https:\/\/doi.org\/10.1038\/s41588-026-02600-3","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]},"assertion":[{"value":"11 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"O.G. received project funding from Bruker Spatial Biology to run the GeoMx experiment. D.M. and T.M.V. are employees of Bruker Spatial Biology. M.A. has research collaborations with GSK and AstraZeneca. J.M.S. declares consultant honorary from Akero, Alentis, Alexion, Altimmune, AstraZeneca, 89Bio, Bionorica, Boehringer Ingelheim, Boston Pharmaceuticals, Gilead Sciences, GSK, HistoIndex, Ipsen, Inventiva Pharma, Madrigal Pharmaceuticals, PRO.MED.CS Praha a.s., Kr\u00edya Therapeutics, Eli Lilly, MSD Sharp & Dohme GmbH, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi and Siemens Healthineers; and speaker honorarium from AbbVie, Boehringer Ingelheim, Gilead Sciences, Ipsen, Eli Lilly, Novo Nordisk, Madrigal Pharmaceuticals, Stockholder options\u2014Hepta Bio. D.T. is a consultant for Inventiva SA and ICON Plc. Q.M.A. received project funding from AstraZeneca, Boehringer Ingelheim and Interecept; is a consultant for Abbvie, Alimentiv, Akero, AstraZeneca, Axcella, 89Bio, Boehringer Ingelheim, Boston Pharaceticals, Corcept Therapeutics, Echosens, Eli Lilly, Gilead, GlaxoSmithKline, HistoIndex, Intercept, Inventiva, Madrigal, Medpace, Merck, Metadeq, Novo Nordisk, PathAI, Pfizer, Pharmanest, Prosciento, Regeneron, Resolution Therapeutics, Roche and Terns; obtained extra funding from Avalere, Catalyst Medical Education, Integritas Communications, Medscape, Novo Nordisk, Springer Healthcare and Elsevier; and is on the advisory board from Medpace and Gilead. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}