title: Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury.
abstract: Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Johanna R
authors.initials: JR
authors.lastname: Schaub
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Yann
authors.initials: Y
authors.lastname: Malato
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Coralie
authors.initials: C
authors.lastname: Gormond
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Department of Surgery, Division of Transplantation, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA; Liver Center, University of California, San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA. Electronic address: willenbringh@stemcell.ucsf.edu.
authors.forename: Holger
authors.initials: H
authors.lastname: Willenbring
mesh_terms: D000818:Animals; D019070:Cell Lineage; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000503:physiopathology*; D022781:Hepatocytes / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008822:Mice, Transgenic