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Nature. 2019 Jul 10. doi: 10.1038/s41586-019-1373-2. [Epub ahead of print]

A human liver cell atlas reveals heterogeneity and epithelial progenitors.

Aizarani N1,2,3, Saviano A4,5,6, Sagar1, Mailly L4,5, Durand S4,5, Herman JS1,2,3, Pessaux P4,5,6, Baumert TF7,8,9, Grün D10,11.

Author information

1
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
2
Faculty of Biology, University of Freiburg, Freiburg, Germany.
3
International Max Planck Research School for Molecular and Cellular Biology (IMPRS-MCB), Freiburg, Germany.
4
Institut National de la Santé et de la Recherche Médicale, Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
5
Université de Strasbourg, Strasbourg, France.
6
Pôle Hepato-digestif, Institut Hopitalo-universitaire, Hôpitaux Universitaires, Strasbourg, France.
7
Institut National de la Santé et de la Recherche Médicale, Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France. thomas.baumert@unistra.fr.
8
Université de Strasbourg, Strasbourg, France. thomas.baumert@unistra.fr.
9
Pôle Hepato-digestif, Institut Hopitalo-universitaire, Hôpitaux Universitaires, Strasbourg, France. thomas.baumert@unistra.fr.
10
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany. gruen@ie-freiburg.mpg.de.
11
CIBSS-Centre for Integrative Biological Signaling Studies, University of Freiburg, Freiburg, Germany. gruen@ie-freiburg.mpg.de.

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.

PMID:
31292543
DOI:
10.1038/s41586-019-1373-2

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