Logo image
Back
Plastic hepatocyte states limit liver cancer development
Journal article   Open access   Peer reviewed

Plastic hepatocyte states limit liver cancer development

Lauren S. Strathearn, Yuki Hayata, Abhinav Illendula, Charles K. Hewett, Mingjia Chen, Guoshun He, Maria Escribano-Cebrian, Brianna Jarboe, Laura Gomez-Tome, Nicola de Prisco, …
Nature communications, v 16(1), 11647
26 Nov 2025
DOI: https://doi.org/10.1038/s41467-025-66568-0
PMID: 41290681
url
https://doi.org/10.1038/s41467-025-66568-0View
Published, Version of Record (VoR) Open

Abstract

Multidisciplinary Sciences Science & Technology Science & Technology - Other Topics
The liver has remarkable regenerative capacity owing to the boundless proliferative potential of hepatocytes. During liver injury, sustained regeneration must be balanced by mechanisms limiting overgrowth and tumorigenesis. Epithelial plasticity is frequently observed during liver damage and is thought to mediate production of biliary epithelial cells (BECs) or hepatocytes, depending on tissue needs. Here we show that hepatocytes persisting in plastic states are present in virtually all liver injury contexts, representing the predominant outcome of hepatocyte reprogramming rather than their full BEC conversion. By developing tools to trap mouse hepatocytes in plastic states in vivo and using models of regeneration and transplantation, we show that plastic hepatocytes are refractory to proliferation cues from the microenvironment. Unlike terminally differentiated hepatocytes, plastic hepatocytes resist proliferation driven by endogenous oncogenic stimuli. Thus, acquisition of plastic states represents a protective mechanism that constrains hepatocyte proliferation, limiting overgrowth and tumorigenesis during liver disease.

Metrics

1 Record Views
1 citations in Web of Science

Details

Logo image