A human liver cell atlas reveals heterogeneity and epithelial progenitors
Top Cited Papers
Open Access
- 10 July 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 572 (7768), 199-204
- https://doi.org/10.1038/s41586-019-1373-2
Abstract
The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, Kupffer cells, and hepatocytes, with transcriptome-wide zonation of some of these populations. We show that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers.Keywords
This publication has 44 references indexed in Scilit:
- Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populationsNature Communications, 2018
- FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq dataNature Methods, 2018
- Metabolic zonation of the liver: The oxygen gradient revisitedRedox Biology, 2017
- Single-cell spatial reconstruction reveals global division of labour in the mammalian liverNature, 2017
- Annual Report to the Nation on the Status of Cancer, 1975‐2012, featuring the increasing incidence of liver cancerCancer, 2016
- Design and Analysis of Single-Cell Sequencing ExperimentsCell, 2015
- Single-cell messenger RNA sequencing reveals rare intestinal cell typesNature, 2015
- Liver RegenerationScience, 1997
- Zonation of Parenchymal and Nonparenchymal Metabolism in LiverAnnual Review of Nutrition, 1996
- Metabolic zonation of the liver: Regulation and implications for liver functionPharmacology & Therapeutics, 1992