Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Autor:	Guilliams M; Laboratory 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., Bonnardel J; Laboratory 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., Haest B; Laboratory 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., Vanderborght B; Hepatology 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., Wagner C; Laboratory 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., Remmerie A; 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., Bujko A; 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., Martens L; Laboratory 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., Thoné T; Laboratory 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., Browaeys R; Data 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., De Ponti FF; 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., Vanneste B; Laboratory 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., Zwicker C; 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., Svedberg FR; Laboratory 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., Vanhalewyn T; Laboratory 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., Gonçalves A; Department 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., Lippens S; Department 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., Devriendt B; Laboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Belgium., Cox E; Laboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Belgium., Ferrero G; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium., Wittamer V; Institut 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., Willaert A; Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Kaptein SJF; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium., Neyts J; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium., Dallmeier K; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium., Geldhof P; Laboratory of Parasitology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium., Casaert S; Laboratory of Parasitology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium., Deplancke B; Laboratory 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., Ten Dijke P; Oncode Institute, Department of Cell and Chemical Biology, Leiden Medical Center, Leiden, Netherlands., Hoorens A; Department of Pathology, Ghent University Hospital, Ghent 9000, Belgium., Vanlander A; Department of General and Hepatopancreatobiliary Surgery and Liver Transplantation, Ghent University Hospital, Ghent 9000, Belgium., Berrevoet F; Department of General and Hepatopancreatobiliary Surgery and Liver Transplantation, Ghent University Hospital, Ghent 9000, Belgium., Van Nieuwenhove Y; Department of Human Structure and Repair, Ghent University Hospital, Ghent 9000, Belgium., Saeys Y; Data 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., Saelens W; Laboratory 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., Van Vlierberghe H; Hepatology Research Unit, Department Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Belgium; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium., Devisscher L; Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center, Ghent University, Belgium., Scott CL; 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. Electronic address: charlotte.scott@ugent.be.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2022 Jan 20; Vol. 185 (2), pp. 379-396.e38. Date of Electronic Publication: 2022 Jan 11.
DOI:	10.1016/j.cell.2021.12.018
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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