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Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Martin Guilliams (UGent) , Johnny Bonnardel (UGent) , Birthe Haest (UGent) , Bart Vanderborght (UGent) , Camille Wagner (UGent) , Anneleen Remmerie, Anna Bujko (UGent) , Liesbet Martens (UGent) , Tinne Thoné (UGent) , Robin Browaeys (UGent) , et al.
(2022) CELL. 185(2). p.379-396
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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.
Keywords
General Biochemistry, Genetics and Molecular Biology, hepatic cells, KUPFFER CELLS, SINGLE, STEATOHEPATITIS, VISUALIZATION, ENDOTHELIUM, FEATURES, LIGANDS, NETWORK, IMAGE

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MLA
Guilliams, Martin, et al. “Spatial Proteogenomics Reveals Distinct and Evolutionarily Conserved Hepatic Macrophage Niches.” CELL, vol. 185, no. 2, 2022, pp. 379–96, doi:10.1016/j.cell.2021.12.018.
APA
Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., … Scott, C. (2022). Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. CELL, 185(2), 379–396. https://doi.org/10.1016/j.cell.2021.12.018
Chicago author-date
Guilliams, Martin, Johnny Bonnardel, Birthe Haest, Bart Vanderborght, Camille Wagner, Anneleen Remmerie, Anna Bujko, et al. 2022. “Spatial Proteogenomics Reveals Distinct and Evolutionarily Conserved Hepatic Macrophage Niches.” CELL 185 (2): 379–96. https://doi.org/10.1016/j.cell.2021.12.018.
Chicago author-date (all authors)
Guilliams, Martin, Johnny Bonnardel, Birthe Haest, Bart Vanderborght, Camille Wagner, Anneleen Remmerie, Anna Bujko, Liesbet Martens, Tinne Thoné, Robin Browaeys, Federico Francesco De Ponti, Bavo Vanneste, Christian Zwicker, Freya Svedberg, Tineke Vanhalewyn, Amanda Gonçalves, Saskia Lippens, Bert Devriendt, Eric Cox, Giuliano Ferrero, Valerie Wittamer, Andy Willaert, Suzanne J.F. Kaptein, Johan Neyts, Kai Dallmeier, Peter Geldhof, Stijn Casaert, Bart Deplancke, Peter ten Dijke, Anne Hoorens, Aude Vanlander, Frederik Berrevoet, Yves Van Nieuwenhove, Yvan Saeys, Wouter Saelens, Hans Van Vlierberghe, Lindsey Devisscher, and Charlotte Scott. 2022. “Spatial Proteogenomics Reveals Distinct and Evolutionarily Conserved Hepatic Macrophage Niches.” CELL 185 (2): 379–396. doi:10.1016/j.cell.2021.12.018.
Vancouver
1.
Guilliams M, Bonnardel J, Haest B, Vanderborght B, Wagner C, Remmerie A, et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. CELL. 2022;185(2):379–96.
IEEE
[1]
M. Guilliams et al., “Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches,” CELL, vol. 185, no. 2, pp. 379–396, 2022.
@article{8738275,
  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.}},
  author       = {{Guilliams, Martin and Bonnardel, Johnny and Haest, Birthe and Vanderborght, Bart and Wagner, Camille and Remmerie, Anneleen and Bujko, Anna and Martens, Liesbet and Thoné, Tinne and Browaeys, Robin and De Ponti, Federico Francesco and Vanneste, Bavo and Zwicker, Christian and Svedberg, Freya and Vanhalewyn, Tineke and Gonçalves, Amanda and Lippens, Saskia and Devriendt, Bert and Cox, Eric and Ferrero, Giuliano and Wittamer, Valerie and Willaert, Andy and Kaptein, Suzanne J.F. and Neyts, Johan and Dallmeier, Kai and Geldhof, Peter and Casaert, Stijn and Deplancke, Bart and ten Dijke, Peter and Hoorens, Anne and Vanlander, Aude and Berrevoet, Frederik and Van Nieuwenhove, Yves and Saeys, Yvan and Saelens, Wouter and Van Vlierberghe, Hans and Devisscher, Lindsey and Scott, Charlotte}},
  issn         = {{0092-8674}},
  journal      = {{CELL}},
  keywords     = {{General Biochemistry,Genetics and Molecular Biology,hepatic cells,KUPFFER CELLS,SINGLE,STEATOHEPATITIS,VISUALIZATION,ENDOTHELIUM,FEATURES,LIGANDS,NETWORK,IMAGE}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{379--396}},
  title        = {{Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches}},
  url          = {{http://doi.org/10.1016/j.cell.2021.12.018}},
  volume       = {{185}},
  year         = {{2022}},
}

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