@article{2872385b742d4d09a22349b08a5b973d,
title = "In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration",
abstract = "The identity of cellular populations that drive liver regeneration after injury is the subject of intense study, and the contributions of polyploid hepatocytes to organ regeneration and homeostasis have not been systematically assessed. Here, we developed a multicolor reporter allele system to genetically label and trace polyploid cells in situ. Multicolored polyploid hepatocytes undergo ploidy reduction and subsequent re-polyploidization after transplantation, providing direct evidence of the hepatocyte ploidy conveyor model. Marker segregation revealed that ploidy reduction rarely involves chromosome missegregation in vivo. We also traced polyploid hepatocytes in several different liver injury models and found robust proliferation in all settings. Importantly, ploidy reduction was seen in all injury models studied. We therefore conclude that polyploid hepatocytes have extensive regenerative capacity in situ and routinely undergo reductive mitoses during regenerative responses.",
keywords = "hepatocyte, lineage tracing, ploidy conveyor, ploidy reduction, polyploidy",
author = "Tomonori Matsumoto and Leslie Wakefield and Tarlow, {Branden David} and Markus Grompe",
note = "Funding Information: The AAV-Ttr-Cre construct was kindly provided by Dr. Holger Willenbring (UCSF). We thank Pamela Canaday (Flow Cytometry Shared Resource at OHSU) for sorting and Stefanie Kaech Petrie (Advanced Light Microscopy Core at OHSU) for microscopy assistance. We thank Dr. Yasmine Akkari for advice on the manuscript. This work was supported by Japan Society for the Promotion of Science overseas research fellowships, KANAE Foundation for the Promotion of Medical Science, Japan (the 46 th KANAE foreign study grants), and NIH grants CA190144 and DK083355 , United States. Funding Information: The AAV-Ttr-Cre construct was kindly provided by Dr. Holger Willenbring (UCSF). We thank Pamela Canaday (Flow Cytometry Shared Resource at OHSU) for sorting and Stefanie Kaech Petrie (Advanced Light Microscopy Core at OHSU) for microscopy assistance. We thank Dr. Yasmine Akkari for advice on the manuscript. This work was supported by Japan Society for the Promotion of Science overseas research fellowships, KANAE Foundation for the Promotion of Medical Science, Japan (the 46th KANAE foreign study grants), and NIH grants CA190144 and DK083355, United States. T.M. and M.G. conceived the project, designed the experiments, and wrote the manuscript. T.M. performed and analyzed most of the experiments. L.W. assisted with the experiments and provided technical help. B.D.T. provided comments and assisted with manuscript preparation. Oregon Health and Science University and Dr. Grompe have significant financial interest in Yecuris, Inc. a company that may have commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by Oregon Health and Science University. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jan,
day = "2",
doi = "10.1016/j.stem.2019.11.014",
language = "English (US)",
volume = "26",
pages = "34--47.e3",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}