ArticleCell2022
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 614 papers, 1 of them a synthesis that pooled it.
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614citing papers in PubMed, 1 pooled it
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Who cites it
614 citing papers in PubMed, 1 synthesis or guideline pooled it, 872 citations in OpenAlex.
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- A refined MASH-HCC model identifies macrophage Gadd45b as a key orchestrator of inflammation-driven neoplastic progression.Experimental & molecular medicine · 2026Article
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554 more citing papers are in PubMed but not listed here.
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Authors and funding
38 authors at 6 institutions in 3 countries.
Martin GuilliamsLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium. Electronic address: martin.guilliams@ugent.be.
Johnny BonnardelLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium.
Birthe HaestLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium.
Bart VanderborghtHepatology Research Unit, Department Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Belgium; Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center, Ghent University, Belgium.
Camille WagnerLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium.
Anneleen RemmerieDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Anna BujkoDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Liesbet MartensLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Tinne ThonéLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Robin BrowaeysData Mining and Modelling for Biomedicine, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Faculty of Science, Ghent University, Ghent, Belgium.
Federico F De PontiDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Bavo VannesteLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Christian ZwickerDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Freya R SvedbergLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium.
Tineke VanhalewynLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Amanda GonçalvesDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; VIB BioImaging Core, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Saskia LippensDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; VIB BioImaging Core, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.
Bert DevriendtLaboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Belgium.
Eric CoxLaboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Belgium.
Giuliano FerreroInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium.
Valerie WittamerInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), Brussels, Belgium; WELBIO, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Andy WillaertCenter for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Suzanne J F KapteinKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium.
Johan NeytsKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium.
Kai DallmeierKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium.
Peter GeldhofLaboratory of Parasitology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Stijn CasaertLaboratory of Parasitology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Bart DeplanckeLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Peter Ten DijkeOncode Institute, Department of Cell and Chemical Biology, Leiden Medical Center, Leiden, Netherlands.
Anne HoorensDepartment of Pathology, Ghent University Hospital, Ghent 9000, Belgium.
Aude VanlanderDepartment of General and Hepatopancreatobiliary Surgery and Liver Transplantation, Ghent University Hospital, Ghent 9000, Belgium.
Frederik BerrevoetDepartment of General and Hepatopancreatobiliary Surgery and Liver Transplantation, Ghent University Hospital, Ghent 9000, Belgium.
Yves Van NieuwenhoveDepartment of Human Structure and Repair, Ghent University Hospital, Ghent 9000, Belgium.
Yvan SaeysData Mining and Modelling for Biomedicine, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Faculty of Science, Ghent University, Ghent, Belgium.
Wouter SaelensLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Hans Van VlierbergheHepatology Research Unit, Department Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Belgium; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium.
Lindsey DevisscherGut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center, Ghent University, Belgium.
Charlotte L ScottDepartment of Biomedical Molecular Biology, Faculty of Science, Ghent University, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium. Electronic address: charlotte.scott@ugent.be.
Ghent University · BEGhent University Hospital · BERega Institute for Medical Research · BESIB Swiss Institute of Bioinformatics · CHUniversité Libre de Bruxelles · BEOncode Institute · NL
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.
Indexed as
Biological EvolutionProteogenomicsAnimalsCell NucleusFatty LiverHepatocytesHomeostasisHumansKupffer CellsLeukocyte Common AntigensLipidsLiverLymphocytesMacrophagesMiceMice, Inbred C57BLLeukocyte Common AntigensLipidsProteomeacross speciesatlasCITE-seqKupffer celllipid-associated macrophagelivermulti-omicNAFLDproteogenomicspatial transcriptomics
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