title: Adult hepatocytes are generated by self-duplication rather than stem cell differentiation.
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.
authors.affiliation: 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.
authors.forename: Kilangsungla
authors.initials: K
authors.lastname: Yanger
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Knigin
authors.affiliation: 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.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zong
authors.affiliation: 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.
authors.forename: Lara
authors.initials: L
authors.lastname: Maggs
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Orthopedics, Gifu University, Gifu City 501-1194, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Immunology and Cancer Research and Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarsky
authors.affiliation: 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.
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
mesh_terms: D000328:Adult; D000818:Animals; D001659:Biliary Tract / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D000229:Dependovirus / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology*