Hybrid Periportal Hepatocytes Regenerate the Injured Liver Without Giving Rise to Cancer

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Aug 16

PMID 26276631

Citations 253

Authors

Joan Font-Burgada

Shabnam Shalapour

Suvasini Ramaswamy

Brian Hsueh

David Rossell

Atsushi Umemura

Koji Taniguchi

Hayato Nakagawa

Mark A Valasek

Li Ye

Janel L Kopp

Maike Sander

Hannah Carter

Karl Deisseroth

Inder M Verma

Michael Karin

Affiliations

Soon will be listed here.

Abstract

Compensatory proliferation triggered by hepatocyte loss is required for liver regeneration and maintenance but also promotes development of hepatocellular carcinoma (HCC). Despite extensive investigation, the cells responsible for hepatocyte restoration or HCC development remain poorly characterized. We used genetic lineage tracing to identify cells responsible for hepatocyte replenishment following chronic liver injury and queried their roles in three distinct HCC models. We found that a pre-existing population of periportal hepatocytes, located in the portal triads of healthy livers and expressing low amounts of Sox9 and other bile-duct-enriched genes, undergo extensive proliferation and replenish liver mass after chronic hepatocyte-depleting injuries. Despite their high regenerative potential, these so-called hybrid hepatocytes do not give rise to HCC in chronically injured livers and thus represent a unique way to restore tissue function and avoid tumorigenesis. This specialized set of pre-existing differentiated cells may be highly suitable for cell-based therapy of chronic hepatocyte-depleting disorders.

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