|
|
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Rockefeller University Press,
0021-9525/1998//1101 $5.00
The Journal of Cell Biology, Volume 143, Number 4,
, 1998 1101-1112
Regular Articles |
Identification of a Bipotential Precursor Cell in Hepatic Cell Lines Derived from Transgenic Mice Expressing Cyto-Met in the Liver
Fondazione "Instituto Pasteur-Cenci Bolognetti," Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, 00161 Roma, Italy
Met murine hepatocyte (MMH) lines were established from livers of transgenic mice expressing constitutively active human Met. These lines harbor two cell types: epithelial cells resembling the parental populations and flattened cells with multiple projections and a dispersed growth habit that are designated palmate. Epithelial cells express the liver-enriched transcription factors HNF4 and HNF1
, and proteins associated with epithelial cell differentiation. Treatments that modulate their differentiation state, including acidic FGF, induce hepatic functions. Palmate cells show none of these properties. However, they can differentiate along the hepatic cell lineage, giving rise to: (a) epithelial cells that express hepatic transcription factors and are competent to express hepatic functions; (b) bile duct-like structures in three-dimensional Matrigel cultures. Derivation of epithelial from palmate cells is confirmed by characterization of the progeny of individually fished cells. Furthermore, karyotype analysis confirms the direction of the phenotypic transition: palmate cells are diploid and the epithelial cells are hypotetraploid. The clonal isolation of the palmate cell, an immortalized nontransformed bipotential cell that does not yet 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.
Key Words: acidic FGF • epithelial morphogenesis • hepatic development and differentiation • HGF/SF • liver-enriched transcription factors
Abbreviations used in this paper: aFGF, acidic FGF; C/EBP, CAAT/enhancer binding protein; CK, cytokeratin; EF, embryonic fibroblast; EHS, Engelbreth-Holm-Swarm; HGF/SF, hepatocyte growth factor/scatter factor; HNF, hepatocyte nuclear factor; LETF, liver-enriched transcription factor; MMH, Met murine hepatocyte; TTR, transthyretin; ZO, zonula occludens.
This work in the Paris laboratory was supported in part by grants from the Biotechnology Programme of the European Economic Community under contract number BIOT CT 93-0103 from the Association pour la Recherche sur le Cancer and La Ligue Nationale contre le Cancer. Work in the Rome laboratory was supported by the AIRC (Associazione Italiana Ricerca sul Cancro), Ministero dell' Universita e Ricerca Scientifica e Tecnologica (MURST), and Centro Nazionale delle Ricerche (CNR) Target project on Biotechnology. A NATO Collaborative Research Grant facilitated the collaboration.
Address all correspondence to Mary C. Weiss, Unité de Génétique de la Différenciation, URA 1773 du CNRS, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Tel.: 33 1 45 68 85 00. Fax: 33 1 40 61 32 31. E-mail: mweiss{at}pasteur.fr
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
