title: Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver.
abstract: The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.
authors.affiliation: 1] Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Medicine and Liver Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Ludan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Fish
authors.affiliation: Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Catriona Y
authors.initials: CY
authors.lastname: Logan
authors.affiliation: Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D004171:Diploidy; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006706:Homeostasis; D008099:Liver / Q000098:blood supply / Q000166:cytology*; D008297:Male; D051379:Mice; D011123:Polyploidy; D012038:Regeneration; D013194:Staining and Labeling; D055153:Stem Cell Niche / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000378:metabolism; D013997:Time Factors; D014680:Veins / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D015415:Biomarkers; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse