Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse embryos

This work shows that hepatic cell lines reproducibly can be derived from E14 embryos of many mouse inbred strains. These bipotential mouse embryonic liver (BMEL) cell lines present a mixed morphology, containing both epithelial and palmate-like cells, and an uncoupled phenotype, expressing hepatocyt...

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Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 2002-10, Vol.36 (4), p.794-804
Hauptverfasser: Strick-Marchand, Hélène, Weiss, Mary C.
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description This work shows that hepatic cell lines reproducibly can be derived from E14 embryos of many mouse inbred strains. These bipotential mouse embryonic liver (BMEL) cell lines present a mixed morphology, containing both epithelial and palmate-like cells, and an uncoupled phenotype, expressing hepatocyte transcription factors (HNF1α, HNF4α, GATA4) but not functions (apolipoproteins, albumin). BMEL cells are bipotential: under inducing conditions they express hepatocyte and bile duct functions. In addition, they can undergo morphogenesis in Matrigel culture to form bile duct units. When returned to basal culture conditions, the differentiated cells revert, within a few days, to an undifferentiated state. The ensemble of markers expressed by BMEL cells implies that they originate from hepatoblasts, the endodermal precursors of the liver. In conclusion, the establishment of a simple and reproducible method to isolate from any mouse embryo bipotential hepatic cell lines that exhibit the properties of transit stem cells provides a novel paradigm for investigation of hepatic cell lineage relationships. (H EPATOLOGY 2002;36:794-804.)
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Psychology ; GATA4 Transcription Factor ; Gene Expression Regulation, Developmental ; Genotype ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 4 ; Hepatocytes - cytology ; Keratins - genetics ; Laminin - pharmacology ; Liver - cytology ; Liver - embryology ; Liver. Bile. 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(H EPATOLOGY 2002;36:794-804.)</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors</subject><subject>Bile Ducts - cytology</subject><subject>Biocompatible Materials - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Collagen - pharmacology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Down-Regulation - physiology</subject><subject>Drug Combinations</subject><subject>Fetus - cytology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GATA4 Transcription Factor</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genotype</subject><subject>Hepatocyte Nuclear Factor 1</subject><subject>Hepatocyte Nuclear Factor 1-alpha</subject><subject>Hepatocyte Nuclear Factor 1-beta</subject><subject>Hepatocyte Nuclear Factor 4</subject><subject>Hepatocytes - cytology</subject><subject>Keratins - genetics</subject><subject>Laminin - pharmacology</subject><subject>Liver - cytology</subject><subject>Liver - embryology</subject><subject>Liver. Bile. Biliary tracts</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Inbred DBA</subject><subject>Nuclear Proteins</subject><subject>Phosphoproteins - genetics</subject><subject>Proteoglycans - pharmacology</subject><subject>Transcription Factors - genetics</subject><subject>Vertebrates: digestive system</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotvCmRvyBW7Zjj8Sx0dUFVqpEhx6txx7zLpK4mBni_bfk3RX2lPFaXx43pnXDyGfGGwZ1OL6aYfTlgPwrWgYF2_IhtVcVULU8JZsgCuoNBP6glyW8gQAWvL2PblgnGvV8mZDdvej37vY9Uh9DAEzjnO0c0wjtaOnQ8rTLv3GEUssNAXaxSnNL0xP-_iMmTrs1-dC0JDTQP_G3lfzYcIlvC9IcejyIZUP5F2wfcGPp3lFHr_fPt7cVQ8_f9zffHuonNCNrOrQdm0dwGKtJAilIDBArlrPOCgrOsk65oVoZMe07zzUUlrXBM1l2zRaXJGvx7VTTn_2WGYzxLJWtCMudYzijCloYAGvj6DLqZSMwUw5DjYfDAOzujWrW7O6NS9ul8Tn0-p9N6A_8yeZC_DlBNjibB-yHV0sZ07oWvN27aiP3KIKD_-7a-5uf9UMRAMS5DmLi8PniNkUF3F06GNGNxuf4qsf-AfhB6dr</recordid><startdate>200210</startdate><enddate>200210</enddate><creator>Strick-Marchand, Hélène</creator><creator>Weiss, Mary C.</creator><general>Elsevier Inc</general><general>W.B. 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Psychology</topic><topic>GATA4 Transcription Factor</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genotype</topic><topic>Hepatocyte Nuclear Factor 1</topic><topic>Hepatocyte Nuclear Factor 1-alpha</topic><topic>Hepatocyte Nuclear Factor 1-beta</topic><topic>Hepatocyte Nuclear Factor 4</topic><topic>Hepatocytes - cytology</topic><topic>Keratins - genetics</topic><topic>Laminin - pharmacology</topic><topic>Liver - cytology</topic><topic>Liver - embryology</topic><topic>Liver. Bile. Biliary tracts</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Inbred DBA</topic><topic>Nuclear Proteins</topic><topic>Phosphoproteins - genetics</topic><topic>Proteoglycans - pharmacology</topic><topic>Transcription Factors - genetics</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strick-Marchand, Hélène</creatorcontrib><creatorcontrib>Weiss, Mary C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strick-Marchand, Hélène</au><au>Weiss, Mary C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse embryos</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2002-10</date><risdate>2002</risdate><volume>36</volume><issue>4</issue><spage>794</spage><epage>804</epage><pages>794-804</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>This work shows that hepatic cell lines reproducibly can be derived from E14 embryos of many mouse inbred strains. These bipotential mouse embryonic liver (BMEL) cell lines present a mixed morphology, containing both epithelial and palmate-like cells, and an uncoupled phenotype, expressing hepatocyte transcription factors (HNF1α, HNF4α, GATA4) but not functions (apolipoproteins, albumin). BMEL cells are bipotential: under inducing conditions they express hepatocyte and bile duct functions. In addition, they can undergo morphogenesis in Matrigel culture to form bile duct units. When returned to basal culture conditions, the differentiated cells revert, within a few days, to an undifferentiated state. The ensemble of markers expressed by BMEL cells implies that they originate from hepatoblasts, the endodermal precursors of the liver. In conclusion, the establishment of a simple and reproducible method to isolate from any mouse embryo bipotential hepatic cell lines that exhibit the properties of transit stem cells provides a novel paradigm for investigation of hepatic cell lineage relationships. 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subjects Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Bile Ducts - cytology
Biocompatible Materials - pharmacology
Biological and medical sciences
Biomarkers
Cell Differentiation
Cell Line
Collagen - pharmacology
DNA-Binding Proteins - genetics
Down-Regulation - physiology
Drug Combinations
Fetus - cytology
Fundamental and applied biological sciences. Psychology
GATA4 Transcription Factor
Gene Expression Regulation, Developmental
Genotype
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 1-beta
Hepatocyte Nuclear Factor 4
Hepatocytes - cytology
Keratins - genetics
Laminin - pharmacology
Liver - cytology
Liver - embryology
Liver. Bile. Biliary tracts
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
Nuclear Proteins
Phosphoproteins - genetics
Proteoglycans - pharmacology
Transcription Factors - genetics
Vertebrates: digestive system
title Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse embryos
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