Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Martin Guilliams, Johnny Bonnardel, Birthe Haest, Bart Vanderborght, Camille Wagner, Anneleen Remmerie, Anna Bujko, Liesbet Martens, Tinne Thoné, Robin Browaeys, Federico F. De Ponti, Bavo Vanneste, Christian Zwicker, Freya R. 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, Charlotte L. Scott

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.

Datasets

1. All cells from human liver dataset
Metadata
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typeSample
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sex
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H0239132 cells
H0623897 cells
H1622272 cells
H1314539 cells
H2310891 cells
H259350 cells
H218524 cells
H388111 cells
H076295 cells
H226077 cells
H375403 cells
H144669 cells
H183013 cells
H101664 cells
H041602 cells
H301480 cells
H11610 cells
H3358 cells
H3211 cells
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Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

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Dataset 1
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Source data

https://cellxgene.cziscience.com/collections/74e10dc4-cbb2-4605-a189-8a1cd8e44d8c

Alias names

GSE192742, PMID35021063, PMC8809252

Cite this study

Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., Bujko, A., Martens, L., Thoné, T., Browaeys, R. and De Ponti, F.F., 2022. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell, 185(2), pp.379-396. https://doi.org/10.1016/j.cell.2021.12.018