Evidence map›Paper›PMID 37228755›Full record

ArticleCell genomics2023

Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential.

Rodrigo Carlessi, Elena Denisenko, Ebru Boslem, Julia Köhn-Gaone, Nathan Main, N Dianah B Abu Bakar, Gayatri D Shirolkar, Matthew Jones, Aaron B Beasley, Daniel Poppe and 15 more

Open access · goldAbstract read
In one paragraph

Article in Cell genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Dysregulated mScience advances · 2026
    Article
  3. Codon-optimizedMolecular therapy. Nucleic acids · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026
    Review
  8. p16Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 9 institutions in 3 countries.

Rodrigo CarlessiCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Elena DenisenkoHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Ebru BoslemCellular & Molecular Metabolism Laboratory, Monash Institute of Pharmacological Sciences, Monash University, Parkville, VIC 3052, Australia.
Julia Köhn-GaoneCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Nathan MainCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
N Dianah B Abu BakarCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Gayatri D ShirolkarCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Matthew JonesHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Aaron B BeasleySchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
Daniel PoppeHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Benjamin J DwyerCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Connie JackamanCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
M Christian TjiamCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Ryan ListerHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Michael KarinDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jonathan A FallowfieldUniversity of Edinburgh Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Timothy J KendallUniversity of Edinburgh Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Stuart J ForbesCentre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Elin S GraySchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
John K OlynykSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
George YeohHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Alistair R R ForrestHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
Grant A RammHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Mark A FebbraioCellular & Molecular Metabolism Laboratory, Monash Institute of Pharmacological Sciences, Monash University, Parkville, VIC 3052, Australia.
Janina E E Tirnitz-ParkerCurtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
The University of Western Australia · AUCurtin University · AUEdith Cowan University · AUCentre for Inflammation Research · GBMonash University · AUMRC Centre for Regenerative Medicine · GBQIMR Berghofer Medical Research Institute · AUThe Kids Research Institute Australia · AUUniversity of California San Diego · US

Funding

Highly penetrant and immunogenic mouse models of non-viral HCC that are suitable for evaluation of immune checkpoint inhibitorsR01CA234128 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 2019 to 2023
$2.7M
NCI NIH HHS R01 CA234128
6 · The paper itself

Abstract

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.

Indexed as

cancer surveillancechronic liver diseasedaHepdisease-associated hepatocyteHCChepatocellular carcinomapre-malignancyprognostic biomarkersnRNA-seq

Identifiers

PMID37228755
PMCPMC10203275
OpenAlexW4365458809

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.