A Human Liver Cell Atlas reveals Heterogeneity and Epithelial Progenitors

By Nadim Aizarani, Antonio Saviano, Sagar, L. Mailly, Sarah C. Durand, J. S. Herman, P. Pessaux, T. Baumert, Dominic Grün. Nature, 2019

957 citations recorded by the source corpus.

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. Single-cell RNA sequencing of cells from healthy human liver, hepatocellular carcinoma and chimaeric mouse liver identifies subtypes of liver cells, epithelial progenitors and differences between healthy and diseased cells.

Subfields: Cancer Research, Hepatology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e8632fee233658d707ad96012c515d8711e028ac

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In Cancer Research

1. Aleksandr Ianevski
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Citations in the corpus

• Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data (2022, methodology): “We fi rst investigated the performance of ScType by re-analyzing a published scRNA-seq study of human liver cells 10 .”
• Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection (2020, methodology): “To assess the cell type specific expression of ACE2,, we first analyzed a published dataset containing scRNA-seq data of the normal liver samples from 9 colorectal patients (GEO124395) [12].”
• Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches (2022, neutral): “Validating this approach, cholangiocytes mapped specifically to the portal zones (Aizarani et al., 2019), while KCs were preferentially located in periportal and mid zones (Bonnardel et al.”