Abstract

The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.

Details

Title
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
Author
MacParland, Sonya A 1 ; Liu, Jeff C 2 ; Xue-Zhong, Ma 3 ; Innes, Brendan T 4   VIAFID ORCID Logo  ; Bartczak, Agata M 3 ; Gage, Blair K 5 ; Manuel, Justin 3 ; Khuu, Nicholas 6 ; Echeverri, Juan 3 ; Linares, Ivan 3 ; Gupta, Rahul 3 ; Cheng, Michael L 7   VIAFID ORCID Logo  ; Liu, Lewis Y 8 ; Camat, Damra 3 ; Chung, Sai W 8 ; Seliga, Rebecca K 3 ; Shao, Zigong 3 ; Lee, Elizabeth 3 ; Ogawa, Shinichiro 5 ; Ogawa, Mina 5   VIAFID ORCID Logo  ; Wilson, Michael D 9   VIAFID ORCID Logo  ; Fish, Jason E 10 ; Selzner, Markus 3 ; Ghanekar, Anand 3 ; Grant, David 3   VIAFID ORCID Logo  ; Greig, Paul 3 ; Sapisochin, Gonzalo 3 ; Selzner, Nazia 3 ; Winegarden, Neil 6   VIAFID ORCID Logo  ; Oyedele Adeyi 11 ; Keller, Gordon 12 ; Bader, Gary D 4   VIAFID ORCID Logo  ; McGilvray, Ian D 3 

1  Multi-Organ Transplant Program, Toronto General Hospital Research Institute, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 
2  The Donnelly Centre, University of Toronto, Toronto, ON, Canada 
3  Multi-Organ Transplant Program, Toronto General Hospital Research Institute, Toronto, ON, Canada 
4  The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada 
5  McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada 
6  Princess Margaret Genomics Centre, University Health Network, Toronto, ON, Canada 
7  Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 
8  Department of Immunology, University of Toronto, Toronto, ON, Canada 
9  Department of Molecular Genetics, University of Toronto, Toronto, Canada; Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada 
10  Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Division of Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON, Canada 
11  Multi-Organ Transplant Program, Toronto General Hospital Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada 
12  McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 
Pages
1-21
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06318-7
ProQuest document ID
2124122135
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.