title: Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice.
abstract: The molecular identification of adult hepatic stem/progenitor cells has been hampered by the lack of truly specific markers. To isolate putative adult liver progenitor cells, we used cell surface-marking antibodies, including MIC1-1C3, to isolate subpopulations of liver cells from normal adult mice or those undergoing an oval cell response and tested their capacity to form bilineage colonies in vitro. Robust clonogenic activity was found to be restricted to a subset of biliary duct cells antigenically defined as CD45(-)/CD11b(-)/CD31(-)/MIC1-1C3(+)/CD133(+)/CD26(-), at a frequency of one of 34 or one of 25 in normal or oval cell injury livers, respectively. Gene expression analyses revealed that Sox9 was expressed exclusively in this subpopulation of normal liver cells and was highly enriched relative to other cell fractions in injured livers. In vivo lineage tracing using Sox9creER(T2)-R26R(YFP) mice revealed that the cells that proliferate during progenitor-driven liver regeneration are progeny of Sox9-expressing precursors. A comprehensive array-based comparison of gene expression in progenitor-enriched and progenitor-depleted cells from both normal and DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine or diethyl1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate)-treated livers revealed new potential regulators of liver progenitors.
authors.affiliation: Oregon Stem Cell Center, Oregon Health and Science University, Portland, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Dorrell
authors.forename: Laura
authors.initials: L
authors.lastname: Erker
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.forename: Janel L
authors.initials: JL
authors.lastname: Kopp
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Canaday
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fox
authors.forename: Olga
authors.initials: O
authors.lastname: Smirnova
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Duncan
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D002999:Clone Cells; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism