A human liver cell atlas reveals heterogeneity and epithelial progenitors

Nadim Aizarani, Antonio Saviano, Sagar, Laurent Mailly, Sarah Durand, Josip S. Herman, Patrick Pessaux, Thomas F. Baumert () and Dominic Grün ()
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Nadim Aizarani: Max-Planck-Institute of Immunobiology and Epigenetics
Antonio Saviano: Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques
Sagar: Max-Planck-Institute of Immunobiology and Epigenetics
Laurent Mailly: Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques
Sarah Durand: Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques
Josip S. Herman: Max-Planck-Institute of Immunobiology and Epigenetics
Patrick Pessaux: Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques
Thomas F. Baumert: Unité 1110, Institut de Recherche sur les Maladies Virales et Hépatiques
Dominic Grün: Max-Planck-Institute of Immunobiology and Epigenetics

Nature, 2019, vol. 572, issue 7768, 199-204

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1373-2

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