IDENTIFICATION OF A BIPOTENTIAL PRECURSOR CELL IN HEPATIC CELL-LINES DERIVED FROM TRANSGENIC MICE EXPRESSING CYTO-MET IN THE LIVER

Citation
Fm. Spagnoli et al., IDENTIFICATION OF A BIPOTENTIAL PRECURSOR CELL IN HEPATIC CELL-LINES DERIVED FROM TRANSGENIC MICE EXPRESSING CYTO-MET IN THE LIVER, The Journal of cell biology, 143(4), 1998, pp. 1101-1112
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology
Journal title
ISSN journal
0021-9525
Volume
143
Issue
4
Year of publication
1998
Pages
1101 - 1112
Database
ISI
SICI code
0021-9525(1998)143:4<1101:IOABPC>2.0.ZU;2-L
Abstract
Met murine hepatocyte (MMH) lines were established from livers of tran sgenic mice expressing constitutively active human Met. These lines ha rbor two cell types: epithelial cells resembling the parental populati ons and flattened cells with multiple projections and a dispersed grow th habit that are designated palmate. Epithelial cells express the liv er-enriched transcription factors HNF4 and HNF1 alpha, and proteins as sociated with epithelial cell differentiation. Treatments that modulat e their differentiation state, including acidic FGF, induce hepatic fu nctions. Palmate cells show none of these properties. However, they ca n differentiate along the hepatic cell lineage, giving rise to: (a) ep ithelial cells that express hepatic transcription factors and are comp etent to express hepatic functions; (b) bile duct-like structures in t hree-dimensional Matrigel cultures. Derivation of epithelial from palm ate cells is confirmed by characterization of the progeny of individua lly fished cells. Furthermore, karyotype analysis confirms the directi on of the phenotypic transition: palmate cells are diploid and the epi thelial cells are hypotetraploid. The clonal isolation of the palmate cell, an immortalized nontransformed bipotential cell that does not ye t express the liver-enriched transcription factors and is a precursor of the epithelial-hepatocyte in MMH lines, provides a new tool for the study of mechanisms controlling liver development.