Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
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 CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By inte...
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| creator | Guilliams, Martin Bonnardel, Johnny Haest, Birthe Vanderborght, Bart Wagner, Camille Remmerie, Anneleen Bujko, Anna Martens, Liesbet Thoné, Tinne Browaeys, Robin De Ponti, Federico Francesco Vanneste, Bavo Zwicker, Christian Svedberg, Freya Vanhalewyn, Tineke Gonçalves, Amanda Lippens, Saskia Devriendt, Bert Cox, Eric Ferrero, Giuliano Wittamer, Valerie Willaert, Andy Kaptein, Suzanne J.F Neyts, Johan Dallmeier, Kai Geldhof, Peter Casaert, Stijn Deplancke, Bart ten Dijke, Peter Hoorens, Anne Vanlander, Aude Berrevoet, Frederik Van Nieuwenhove, Yves Saeys, Yvan Saelens, Wouter Van Vlierberghe, Hans Devisscher, Lindsey Scott, Charlotte |
| description | 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 CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multiomic 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. |
| format | Article |
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Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multiomic 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.</description><identifier>ISSN: 0092-8674</identifier><identifier>ISSN: 1097-4172</identifier><language>eng</language><subject>Biology and Life Sciences ; ENDOTHELIUM ; FEATURES ; General Biochemistry ; Genetics and Molecular Biology ; hepatic cells ; KUPFFER CELLS ; LIGANDS ; Mathematics and Statistics ; Medicine and Health Sciences ; NETWORK ; SINGLE ; STEATOHEPATITIS ; VISUALIZATION</subject><creationdate>2022</creationdate><rights>Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,4010,27837</link.rule.ids></links><search><creatorcontrib>Guilliams, Martin</creatorcontrib><creatorcontrib>Bonnardel, Johnny</creatorcontrib><creatorcontrib>Haest, Birthe</creatorcontrib><creatorcontrib>Vanderborght, Bart</creatorcontrib><creatorcontrib>Wagner, Camille</creatorcontrib><creatorcontrib>Remmerie, Anneleen</creatorcontrib><creatorcontrib>Bujko, Anna</creatorcontrib><creatorcontrib>Martens, Liesbet</creatorcontrib><creatorcontrib>Thoné, Tinne</creatorcontrib><creatorcontrib>Browaeys, Robin</creatorcontrib><creatorcontrib>De Ponti, Federico Francesco</creatorcontrib><creatorcontrib>Vanneste, Bavo</creatorcontrib><creatorcontrib>Zwicker, Christian</creatorcontrib><creatorcontrib>Svedberg, Freya</creatorcontrib><creatorcontrib>Vanhalewyn, Tineke</creatorcontrib><creatorcontrib>Gonçalves, Amanda</creatorcontrib><creatorcontrib>Lippens, Saskia</creatorcontrib><creatorcontrib>Devriendt, Bert</creatorcontrib><creatorcontrib>Cox, Eric</creatorcontrib><creatorcontrib>Ferrero, Giuliano</creatorcontrib><creatorcontrib>Wittamer, Valerie</creatorcontrib><creatorcontrib>Willaert, Andy</creatorcontrib><creatorcontrib>Kaptein, Suzanne J.F</creatorcontrib><creatorcontrib>Neyts, Johan</creatorcontrib><creatorcontrib>Dallmeier, Kai</creatorcontrib><creatorcontrib>Geldhof, Peter</creatorcontrib><creatorcontrib>Casaert, Stijn</creatorcontrib><creatorcontrib>Deplancke, Bart</creatorcontrib><creatorcontrib>ten Dijke, Peter</creatorcontrib><creatorcontrib>Hoorens, Anne</creatorcontrib><creatorcontrib>Vanlander, Aude</creatorcontrib><creatorcontrib>Berrevoet, Frederik</creatorcontrib><creatorcontrib>Van Nieuwenhove, Yves</creatorcontrib><creatorcontrib>Saeys, Yvan</creatorcontrib><creatorcontrib>Saelens, Wouter</creatorcontrib><creatorcontrib>Van Vlierberghe, Hans</creatorcontrib><creatorcontrib>Devisscher, Lindsey</creatorcontrib><creatorcontrib>Scott, Charlotte</creatorcontrib><title>Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches</title><description>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 CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multiomic 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.</description><subject>Biology and Life Sciences</subject><subject>ENDOTHELIUM</subject><subject>FEATURES</subject><subject>General Biochemistry</subject><subject>Genetics and Molecular Biology</subject><subject>hepatic cells</subject><subject>KUPFFER CELLS</subject><subject>LIGANDS</subject><subject>Mathematics and Statistics</subject><subject>Medicine and Health Sciences</subject><subject>NETWORK</subject><subject>SINGLE</subject><subject>STEATOHEPATITIS</subject><subject>VISUALIZATION</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ADGLB</sourceid><recordid>eNqdjEsKwjAUALNQ8HuHdwEhtMbWtSjudW14TZ_NkzQpSSx4exU8gatZDDMTMZdyX2zqXbWdiUVKDyllrZSai9tlwMzoYIghU-jIh55NgkgjoUvQcsrsTQb0LdAY3DNz8BjZvcAEnyiO1IKl78VAjyaGwWJH4NlYSisxvX82tP5xKYrT8Xo4bzpLPmvHTSSDWQdkjdFYHkk_u69qSNdVWReVKv-K3jQ1Uh0</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Guilliams, Martin</creator><creator>Bonnardel, Johnny</creator><creator>Haest, Birthe</creator><creator>Vanderborght, Bart</creator><creator>Wagner, Camille</creator><creator>Remmerie, Anneleen</creator><creator>Bujko, Anna</creator><creator>Martens, Liesbet</creator><creator>Thoné, Tinne</creator><creator>Browaeys, Robin</creator><creator>De Ponti, Federico Francesco</creator><creator>Vanneste, Bavo</creator><creator>Zwicker, Christian</creator><creator>Svedberg, Freya</creator><creator>Vanhalewyn, Tineke</creator><creator>Gonçalves, Amanda</creator><creator>Lippens, Saskia</creator><creator>Devriendt, Bert</creator><creator>Cox, Eric</creator><creator>Ferrero, Giuliano</creator><creator>Wittamer, Valerie</creator><creator>Willaert, Andy</creator><creator>Kaptein, Suzanne J.F</creator><creator>Neyts, Johan</creator><creator>Dallmeier, Kai</creator><creator>Geldhof, Peter</creator><creator>Casaert, Stijn</creator><creator>Deplancke, Bart</creator><creator>ten Dijke, Peter</creator><creator>Hoorens, Anne</creator><creator>Vanlander, Aude</creator><creator>Berrevoet, Frederik</creator><creator>Van Nieuwenhove, Yves</creator><creator>Saeys, Yvan</creator><creator>Saelens, Wouter</creator><creator>Van Vlierberghe, Hans</creator><creator>Devisscher, Lindsey</creator><creator>Scott, Charlotte</creator><scope>ADGLB</scope></search><sort><creationdate>2022</creationdate><title>Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches</title><author>Guilliams, Martin ; Bonnardel, Johnny ; Haest, Birthe ; Vanderborght, Bart ; Wagner, Camille ; Remmerie, Anneleen ; Bujko, Anna ; Martens, Liesbet ; Thoné, Tinne ; Browaeys, Robin ; De Ponti, Federico Francesco ; Vanneste, Bavo ; Zwicker, Christian ; Svedberg, Freya ; Vanhalewyn, Tineke ; Gonçalves, Amanda ; Lippens, Saskia ; Devriendt, Bert ; Cox, Eric ; Ferrero, Giuliano ; Wittamer, Valerie ; Willaert, Andy ; Kaptein, Suzanne J.F ; Neyts, Johan ; Dallmeier, Kai ; Geldhof, Peter ; Casaert, Stijn ; Deplancke, Bart ; ten Dijke, Peter ; Hoorens, Anne ; Vanlander, Aude ; Berrevoet, Frederik ; Van Nieuwenhove, Yves ; Saeys, Yvan ; Saelens, Wouter ; Van Vlierberghe, Hans ; Devisscher, Lindsey ; Scott, Charlotte</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-ghent_librecat_oai_archive_ugent_be_87382753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biology and Life Sciences</topic><topic>ENDOTHELIUM</topic><topic>FEATURES</topic><topic>General Biochemistry</topic><topic>Genetics and Molecular Biology</topic><topic>hepatic cells</topic><topic>KUPFFER CELLS</topic><topic>LIGANDS</topic><topic>Mathematics and Statistics</topic><topic>Medicine and Health Sciences</topic><topic>NETWORK</topic><topic>SINGLE</topic><topic>STEATOHEPATITIS</topic><topic>VISUALIZATION</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guilliams, Martin</creatorcontrib><creatorcontrib>Bonnardel, Johnny</creatorcontrib><creatorcontrib>Haest, Birthe</creatorcontrib><creatorcontrib>Vanderborght, Bart</creatorcontrib><creatorcontrib>Wagner, Camille</creatorcontrib><creatorcontrib>Remmerie, Anneleen</creatorcontrib><creatorcontrib>Bujko, Anna</creatorcontrib><creatorcontrib>Martens, Liesbet</creatorcontrib><creatorcontrib>Thoné, Tinne</creatorcontrib><creatorcontrib>Browaeys, Robin</creatorcontrib><creatorcontrib>De Ponti, Federico Francesco</creatorcontrib><creatorcontrib>Vanneste, Bavo</creatorcontrib><creatorcontrib>Zwicker, Christian</creatorcontrib><creatorcontrib>Svedberg, Freya</creatorcontrib><creatorcontrib>Vanhalewyn, Tineke</creatorcontrib><creatorcontrib>Gonçalves, Amanda</creatorcontrib><creatorcontrib>Lippens, Saskia</creatorcontrib><creatorcontrib>Devriendt, Bert</creatorcontrib><creatorcontrib>Cox, Eric</creatorcontrib><creatorcontrib>Ferrero, Giuliano</creatorcontrib><creatorcontrib>Wittamer, Valerie</creatorcontrib><creatorcontrib>Willaert, Andy</creatorcontrib><creatorcontrib>Kaptein, Suzanne J.F</creatorcontrib><creatorcontrib>Neyts, Johan</creatorcontrib><creatorcontrib>Dallmeier, Kai</creatorcontrib><creatorcontrib>Geldhof, Peter</creatorcontrib><creatorcontrib>Casaert, Stijn</creatorcontrib><creatorcontrib>Deplancke, Bart</creatorcontrib><creatorcontrib>ten Dijke, Peter</creatorcontrib><creatorcontrib>Hoorens, Anne</creatorcontrib><creatorcontrib>Vanlander, Aude</creatorcontrib><creatorcontrib>Berrevoet, Frederik</creatorcontrib><creatorcontrib>Van Nieuwenhove, Yves</creatorcontrib><creatorcontrib>Saeys, Yvan</creatorcontrib><creatorcontrib>Saelens, Wouter</creatorcontrib><creatorcontrib>Van Vlierberghe, Hans</creatorcontrib><creatorcontrib>Devisscher, Lindsey</creatorcontrib><creatorcontrib>Scott, Charlotte</creatorcontrib><collection>Ghent University Academic Bibliography</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guilliams, Martin</au><au>Bonnardel, Johnny</au><au>Haest, Birthe</au><au>Vanderborght, Bart</au><au>Wagner, Camille</au><au>Remmerie, Anneleen</au><au>Bujko, Anna</au><au>Martens, Liesbet</au><au>Thoné, Tinne</au><au>Browaeys, Robin</au><au>De Ponti, Federico Francesco</au><au>Vanneste, Bavo</au><au>Zwicker, Christian</au><au>Svedberg, Freya</au><au>Vanhalewyn, Tineke</au><au>Gonçalves, Amanda</au><au>Lippens, Saskia</au><au>Devriendt, Bert</au><au>Cox, Eric</au><au>Ferrero, Giuliano</au><au>Wittamer, Valerie</au><au>Willaert, Andy</au><au>Kaptein, Suzanne J.F</au><au>Neyts, Johan</au><au>Dallmeier, Kai</au><au>Geldhof, Peter</au><au>Casaert, Stijn</au><au>Deplancke, Bart</au><au>ten Dijke, Peter</au><au>Hoorens, Anne</au><au>Vanlander, Aude</au><au>Berrevoet, Frederik</au><au>Van Nieuwenhove, Yves</au><au>Saeys, Yvan</au><au>Saelens, Wouter</au><au>Van Vlierberghe, Hans</au><au>Devisscher, Lindsey</au><au>Scott, Charlotte</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches</atitle><date>2022</date><risdate>2022</risdate><issn>0092-8674</issn><issn>1097-4172</issn><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 CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multiomic 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.</abstract><oa>free_for_read</oa></addata></record> |
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| source | Ghent University Academic Bibliography; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Biology and Life Sciences ENDOTHELIUM FEATURES General Biochemistry Genetics and Molecular Biology hepatic cells KUPFFER CELLS LIGANDS Mathematics and Statistics Medicine and Health Sciences NETWORK SINGLE STEATOHEPATITIS VISUALIZATION |
| title | Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches |
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