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research article

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Guilliams, Martin
•
Bonnardel, Johnny
•
Haest, Birthe
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January 20, 2022
Cell

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.

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Type
research article
DOI
10.1016/j.cell.2021.12.018
Web of Science ID

WOS:000747432800002

Author(s)
Guilliams, Martin
Bonnardel, Johnny
Haest, Birthe
Vanderborght, Bart
Wagner, Camille
Remmerie, Anneleen
Bujko, Anna
Martens, Liesbet
Thone, Tinne
Browaeys, Robin
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Date Issued

2022-01-20

Publisher

CELL PRESS

Published in
Cell
Volume

185

Issue

2

Start page

379

End page
Subjects

Biochemistry & Molecular Biology

•

Cell Biology

•

hepatic cells

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kupffer cells

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single

•

steatohepatitis

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visualization

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endothelium

•

features

•

ligands

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network

•

image

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPDEPLA  
Available on Infoscience
February 14, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/185437
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