@article{6e99772f203b4dfb930dc67b0d6d29b5,
title = "Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer",
abstract = "Summary 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.",
author = "Joan Font-Burgada and Shabnam Shalapour and Suvasini Ramaswamy and Brian Hsueh and David Rossell and Atsushi Umemura and Koji Taniguchi and Hayato Nakagawa and Valasek, {Mark A.} and Li Ye and Kopp, {Janel L.} and Maike Sander and Hannah Carter and Karl Deisseroth and Verma, {Inder M.} and Michael Karin",
note = "Funding Information: We thank Drs. D. Brenner, T. Kissileva, M. Grompe, and G. Napolitano for comments, M. Vasseur-Cognet for TTR-Cre ERT mice, P. Chambon for Alb-Cre ERT , and W. Sandgren for MUP-uPA mice. Technical support was provided by the UCSD Neuroscience Microscopy Shared Facility (P30 NS047101), the IGM Genomics Center, human stem cell core facility, and the Vector Core Developmental Lab. J.F.-B. was supported by CIRM Training Grant II (TG2-01154); A.U. by a Global Grant Scholarship from The Rotary Foundation; K.T. by a postdoctoral fellowship for Research Abroad, Research Fellowship for Young Scientists from the JSPS, and the Uehara Memorial Foundation Fellowship; S.S. by the DFG and a CRI-Irvington fellowship; and H.N. by the Japanese Society of Gastroenterology, The Tokyo Society of Medical Sciences, and Kanae Foundation. Research was supported by NIH grants CA118165 and CA155120 and the Superfund basic research program (ES010337) to M.K., who holds the Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases and is an ACS Research Professor, and NIH grants HL053670 and AI048034, Cancer Ctr Core Grant (P30 CA014195-38), the Frances C. Berger Foundation, and Leona M. and Harry B. Helmsley Charitable Trust grant 2012-PG-MED002 to I.M.V. M.S. was supported by NIH grants DK078803 and DK068471, and J.L.K. by NIH grant F32CA136124 and an Advanced Postdoctoral Fellowship from the JDRF. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = aug,
day = "17",
doi = "10.1016/j.cell.2015.07.026",
language = "English",
volume = "162",
pages = "766--779",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}
