TY - UNPB
T1 - Single Nucleus RNA Sequencing of Pre-Malignant Liver Reveals Disease-Associated Hepatocyte State with HCC Prognostic Potential
AU - Carlessi, Rodrigo
AU - Denisenko, Elena
AU - Boslem, Ebru
AU - Koehn-Galone, Julia
AU - Main, Nathan
AU - Abu Bakar, N. Dianah B.
AU - Shirolkar, Gayatri D.
AU - Jones, Matt
AU - Poppe, Daniel
AU - Dwyer, Benjamin J.
AU - Jackaman, Connie
AU - Tjiam, Christian
AU - Lister, Ryan
AU - Karin, Michael
AU - Fallowfield, Jonathan A.
AU - Kendall, Timothy J.
AU - Forbes, Stuart J.
AU - Olyny, John K.
AU - Yeoh, George
AU - Forrest, Alistair
AU - Ramm, Grant A.
AU - Febbraio, Mark A.
AU - Tirnitz-Parker, Nina
PY - 2022/3/27
Y1 - 2022/3/27
N2 - Current approaches to stage chronic liver diseases have limited utility to directly predict liver cancer risk. Here, we employed single nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and chronically injured pre-malignant livers using two distinct mouse models. Analysis of 40,748 hepatic nuclei unraveled a previously uncharacterized disease-associated hepatocyte transcriptional state (daHep). These cells were absent in healthy livers, but were increasingly prevalent as chronic liver disease progressed towards hepatocarcinogenesis. Gene expression deconvolution of 1,439 human liver transcriptomes from publicly available datasets revealed that daHep frequencies highly correlate with current histopathological liver disease staging systems. Importantly, we show that high daHep levels precede carcinogenesis in mice and humans and predict a higher risk of hepatocellular carcinoma (HCC) development. This novel transcriptional signature with diagnostic and, more importantly, prognostic significance has the potential to change the way chronic liver disease patients are staged, surveilled and risk-stratified.
AB - Current approaches to stage chronic liver diseases have limited utility to directly predict liver cancer risk. Here, we employed single nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and chronically injured pre-malignant livers using two distinct mouse models. Analysis of 40,748 hepatic nuclei unraveled a previously uncharacterized disease-associated hepatocyte transcriptional state (daHep). These cells were absent in healthy livers, but were increasingly prevalent as chronic liver disease progressed towards hepatocarcinogenesis. Gene expression deconvolution of 1,439 human liver transcriptomes from publicly available datasets revealed that daHep frequencies highly correlate with current histopathological liver disease staging systems. Importantly, we show that high daHep levels precede carcinogenesis in mice and humans and predict a higher risk of hepatocellular carcinoma (HCC) development. This novel transcriptional signature with diagnostic and, more importantly, prognostic significance has the potential to change the way chronic liver disease patients are staged, surveilled and risk-stratified.
UR - https://www.biorxiv.org/content/10.1101/2022.03.25.485695v1
M3 - Preprint
BT - Single Nucleus RNA Sequencing of Pre-Malignant Liver Reveals Disease-Associated Hepatocyte State with HCC Prognostic Potential
PB - bioRxiv
ER -