title: A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver.
abstract: Cells with slow proliferation kinetics that retain the nuclear label over long time periods-the label-retaining cells (LRCs)-represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells.
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Janeli
authors.initials: J
authors.lastname: Viil
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Mariliis
authors.initials: M
authors.lastname: Klaas
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Kadri
authors.initials: K
authors.lastname: Valter
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Denis
authors.initials: D
authors.lastname: Belitškin
authors.affiliation: Department of Pathology and Immunology, Medical School, University of Geneva, Geneva, Switzerland.
authors.forename: Sten
authors.initials: S
authors.lastname: Ilmjärv
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.|Karolinska Institutet, Stockholm, Sweden.
authors.forename: Viljar
authors.initials: V
authors.lastname: Jaks
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000293:injuries / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058948:Cell Tracking / Q000379:methods; D004847:Epithelial Cells / Q000166:cytology; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000254:growth & development / Q000293:injuries; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*