Single cell transcriptomics of Atlantic salmon (Salmo salar L.) liver reveals cellular heterogeneity and immunological responses to challenge by Aeromonas salmonicida.

Richard S Taylor, Rose Ruiz Daniels, Ross Dobie, Shahmir Naseer, Thomas C Clark, Neil C Henderson, Pierre Boudinot, Samuel A M Martin, Daniel J Macqueen

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The liver is a multitasking organ with essential functions for vertebrate health spanning metabolism and immunity. In contrast to mammals, our understanding of liver cellular heterogeneity and its role in regulating immunological status remains poorly defined in fishes. Addressing this knowledge gap, we generated a transcriptomic atlas of 47,432 nuclei isolated from the liver of Atlantic salmon ( Salmo salar L.) contrasting control fish with those challenged with a pathogenic strain of Aeromonas salmonicida, a problematic bacterial pathogen in global aquaculture. We identified the major liver cell types and their sub-populations, revealing poor conservation of many hepatic cell marker genes utilized in mammals, while identifying novel heterogeneity within the hepatocyte, lymphoid, and myeloid lineages. This included polyploid hepatocytes, multiple T cell populations including γδ T cells, and candidate populations of monocytes/macrophages and dendritic cells. A dominant hepatocyte population radically remodeled its transcriptome following infection to activate the acute phase response and other defense functions, while repressing routine functions such as metabolism. These defense-specialized hepatocytes showed strong activation of genes controlling protein synthesis and secretion, presumably to support the release of acute phase proteins into circulation. The infection response further involved up-regulation of numerous genes in an immune-cell specific manner, reflecting functions in pathogen recognition and killing, antigen presentation, phagocytosis, regulation of inflammation, B cell differentiation and T cell activation. Overall, this study greatly enhances our understanding of the multifaceted role played by liver immune and non-immune cells in host defense and metabolic remodeling following infection and provides many novel cell-specific marker genes to empower future studies of this organ in fishes.

Original languageEnglish
Article number984799
Number of pages17
JournalFrontiers in Immunology
Publication statusPublished - 24 Aug 2022

Bibliographical note

This study was funded by grants from the Scottish Universities Life Sciences Alliance (Technology Seed Funding Call), the University of Edinburgh’s Data Driven Innovation Initiative (Scottish Funding Council Beacon ‘Building Back Better’ Call), and the Biotechnology and Biological Sciences Research Council, including the institutional strategic programme grants BBS/E/D/10002071 and BBS/E/D/20002174 and the responsive mode grant BB/W005859/1. NH is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (ref. 219542/Z/19/Z).

Data Availability Statement

All data generated in this study has been made available in the GEO database ( Accession: GSE207655.


  • Aeromonas salmonicida
  • Animals
  • Biomarkers
  • Hepatocytes
  • Liver
  • Mammals
  • Salmo salar/genetics
  • Transcriptome


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