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Cell Stem Cell. 2014 Sep 4;15(3):340-349. doi: 10.1016/j.stem.2014.06.003. Epub 2014 Aug 14.

Adult hepatocytes are generated by self-duplication rather than stem cell differentiation.

Author information

1
Department of Medicine, Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
2
Department of Immunology and Cancer Research and Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
3
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
4
Department of Orthopedics, Gifu University, Gifu City 501-1194, Japan.
5
Department of Immunology and Cancer Research and Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
6
Department of Medicine, Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: bstanger@exchange.upenn.edu.

Abstract

The liver is thought to utilize facultative stem cells, also known as "oval cells" or "atypical ductal cells" (ADCs), for regeneration following various types of injury. However, this notion has been based largely on in vitro studies and transplantation models; where lineage tracing has been used, results have been conflicting and effect sizes have been small. Here, we used genetic and nucleoside analog-based tools to mark and track the origin and contribution of various cell populations to liver regeneration in vivo following several ADC-inducing insults. We report that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.

PMID:
25130492
PMCID:
PMC4505916
DOI:
10.1016/j.stem.2014.06.003
[Indexed for MEDLINE]
Free PMC Article

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