CC BY-NC-ND 4.0 · Semin Liver Dis 2022; 42(03): 250-270
DOI: 10.1055/s-0042-1755272
Review Article

Unraveling the Complexity of Liver Disease One Cell at a Time

Jawairia Atif
1   Ajmera Transplant Centre, Schwartz Reisman Liver Research Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
2   Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
,
Cornelia Thoeni
3   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
,
Gary D. Bader*
4   Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
5   The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
,
Ian D. McGilvray*
1   Ajmera Transplant Centre, Schwartz Reisman Liver Research Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
,
Sonya A. MacParland*
1   Ajmera Transplant Centre, Schwartz Reisman Liver Research Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
2   Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
3   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
› Author Affiliations
Funding This study was funded by the Canadian Institutes for Health Research, (grant no.: 162098) and Chan Zuckerberg Initiative, (grant no.: CZF2019-002429).


Abstract

The human liver is a complex organ made up of multiple specialized cell types that carry out key physiological functions. An incomplete understanding of liver biology limits our ability to develop therapeutics to prevent chronic liver diseases, liver cancers, and death as a result of organ failure. Recently, single-cell modalities have expanded our understanding of the cellular phenotypic heterogeneity and intercellular cross-talk in liver health and disease. This review summarizes these findings and looks forward to highlighting new avenues for the application of single-cell genomics to unravel unknown pathogenic pathways and disease mechanisms for the development of new therapeutics targeting liver pathology. As these technologies mature, their integration into clinical data analysis will aid in patient stratification and in developing treatment plans for patients suffering from liver disease.

Abbreviations

ALD, alcoholic liver disease; CLD, chronic liver disease; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HSC, hepatic stellate cells; ICC, intrahepatic cholangiocarcinoma; IPSC, induced pluripotent stem cell; KC, Kupffer cells; LSECs, liver sinusoidal endothelial cells; miRNA, microRNA; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; scRNA-seq, single-cell RNA sequencing; snRNA-seq, single-nucleus RNA sequencing; TAM, tumor-associated macrophages.


* These authors contributed equally to this research.




Publication History

Article published online:
25 August 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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