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
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.