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Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer

Item Type:Article
Title:Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer
Creators Name:Font-Burgada, J., Shalapour, S., Ramaswamy, S., Hsueh, B., Rossell, D., Umemura, A., Taniguchi, K., Nakagawa, H., Valasek, M.A., Ye, L., Kopp, J.L., Sander, M., Carter, H., Deisseroth, K., Verma, I.M. and Karin, M.
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.
Keywords:Bile Ducts, Cell Proliferation, Cell Transplantation, Hepatocytes, Liver, Liver Neoplasms, Regeneration, SOX9 Transcription Factor, Transcriptome, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:162
Number:4
Page Range:766-79
Date:13 August 2015
Additional Information:Copyright © 2015 Elsevier Inc. All rights reserved.
Official Publication:https://doi.org/10.1016/j.cell.2015.07.026
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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