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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 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-ta

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Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Guilliams M, Bonnardel J, Haest B, Vanderborght B, Wagner C, Remmerie A, Bujko A, Martens L, Thoné T, Browaeys R, De Ponti FF, Vanneste B, Zwicker C, Svedberg FR, Vanhalewyn T, Gonçalves A, Lippens S, Devriendt B, Cox E, Ferrero G, Wittamer V, Willaert A, Kaptein SJF, Neyts J, Dallmeier K, Geldhof P, Casaert S, Deplancke B, Ten Dijke P, Hoorens A, Vanlander A, Berrevoet F, Van Nieuwenhove Y, Saeys Y, Saelens W, Van Vlierberghe H, Devisscher L, Scott CL. (2022). Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell. PMID 35021063 · PMC8809252 · DOI 10.1016/j.cell.2021.12.018
  • 证据类型：PRIMARY_RESEARCH
  • 主题：spatial-omics
  • 被引次数（采集时）：833
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/35021063)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    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.

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    Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. · GeniOmics