title: Murine Sca1(+)Lin(-) bone marrow contains an endodermal precursor population that differentiates into hepatocytes.
abstract: The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1(+) subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Suh Youn
authors.initials: SY
authors.lastname: Shon
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Myung Won
authors.initials: MW
authors.lastname: Seo
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hak Mo
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ju-Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000067696:Ataxin-1; C000593750:Atxn1 protein, mouse