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Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice

Item Type:Article
Title:Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice
Creators Name:Dorrell, C. and Erker, L. and Schug, J. and Kopp, J.L. and Canaday, P.S. and Fox, A.J. and Smirnova, O. and Duncan, A.W. and Finegold, M.J. and Sander, M. and Kaestner, K.H. and Grompe, M.
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.
Keywords:Liver Progenitor, FACS, Microarray, Sox9, Animals, Mice
Source:Genes & Development
Publisher:Cold Spring Harbor Laboratory Press
Page Range:1193-203
Date:1 June 2011
Official Publication:https://doi.org/10.1101/gad.2029411
PubMed:View item in PubMed

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