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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential
Cell Genomics, Volume 3, No. 5, Article 100301, Year 2023
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Description
Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state. These cells were absent in healthy livers but increasingly prevalent as chronic liver disease progressed. Copy number variation (CNV) analysis of microdissected tissue demonstrated that daHep-enriched regions are riddled with structural variants, suggesting these cells represent a pre-malignant intermediary. Integrated analysis of three recent human snRNA-seq datasets confirmed the presence of a similar phenotype in human chronic liver disease and further supported its enhanced mutational burden. Importantly, we show that high daHep levels precede carcinogenesis and predict a higher risk of hepatocellular carcinoma development. These findings may change the way chronic liver disease patients are staged, surveilled, and risk stratified. © 2023 The Author(s)
Authors & Co-Authors
Denisenko, Elena
Australia, Perth
Queen Elizabeth Ii Medical Centre Trust
Jackaman, Connie
Australia, Perth
Curtin University
Karin, Michael
United States, La Jolla
University of California, San Diego
Fallowfield, Jonathan Andrew
United Kingdom, Edinburgh
The University of Edinburgh
Kendall, Timothy J.
United Kingdom, Edinburgh
The University of Edinburgh
Gray, Elin Solomonovna
Australia, Perth
Edith Cowan University
Forrest, Alistair R.R.
Australia, Perth
Queen Elizabeth Ii Medical Centre Trust
Statistics
Citations: 3
Authors: 7
Affiliations: 8
Identifiers
Doi:
10.1016/j.xgen.2023.100301
ISSN:
2666979X
Research Areas
Cancer