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Article: Murine gallbladder epithelial cells can differentiate into hepatocyte-like cells in vitro

TitleMurine gallbladder epithelial cells can differentiate into hepatocyte-like cells in vitro
Authors
KeywordsBiliary epithelium
Cell culture
Stem cells
Transdifferentiation
Transgenic mice
Issue Date2007
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/
Citation
American Journal Of Physiology - Gastrointestinal And Liver Physiology, 2007, v. 293 n. 5, p. G944-G955 How to Cite?
AbstractWe determined whether extrahepatic biliary epithelial cells can differentiate into cells with phenotypic features of hepatocytes. Gallbladders were removed from transgenic mice expressing hepatocyte-specific β-galactosidase (β-Gal) and cultured under standard conditions and under experimental conditions designed to induce differentiation into a hepatocyte-like phenotype. Gallbladder epithelial cells (GBEC) cultured under standard conditions exhibited no β-Gal activity. β-Gal expression was prominent in 50% of cells cultured under experimental conditions. Similar morphological changes were observed in GBEC from green fluorescent protein transgenic mice cultured under experimental conditions. These cells showed higher levels of mRNA for genes expressed in hepatocytes, but not in GBEC, including aldolase B, albumin, hepatocyte nuclear factor-4α, aldehyde dehydrogenase 1, and glutamine synthetase, and they synthesized bile acids. Additional functional evidence of a hepatocyte-like phenotype included LDL uptake and enhanced benzodiazepine metabolism. Connexin-32 expression was evident in murine hepatocytes and in cells cultured under experimental conditions, but not in cells cultured under standard conditions. Notch 1, 2, and 3 and Notch ligand Jagged 1 mRNAs were downregulated in these cells compared with cells cultured under standard conditions. CD34, α-fetoprotein, and Sca-1 mRNA were not expressed in cells cultured under standard conditions, suggesting that the hepatocyte-like cells did not arise from hematopoietic stem cells or oval cells. These results point to future avenues for investigation into the potential use of GBEC in the treatment of liver disease.
Persistent Identifierhttp://hdl.handle.net/10722/92510
ISSN
2015 Impact Factor: 3.297
2015 SCImago Journal Rankings: 1.936
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKuver, Ren_HK
dc.contributor.authorSavard, CEen_HK
dc.contributor.authorSung, KLen_HK
dc.contributor.authorHaigh, WGen_HK
dc.contributor.authorLee, SPen_HK
dc.date.accessioned2010-09-17T10:48:26Z-
dc.date.available2010-09-17T10:48:26Z-
dc.date.issued2007en_HK
dc.identifier.citationAmerican Journal Of Physiology - Gastrointestinal And Liver Physiology, 2007, v. 293 n. 5, p. G944-G955en_HK
dc.identifier.issn0193-1857en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92510-
dc.description.abstractWe determined whether extrahepatic biliary epithelial cells can differentiate into cells with phenotypic features of hepatocytes. Gallbladders were removed from transgenic mice expressing hepatocyte-specific β-galactosidase (β-Gal) and cultured under standard conditions and under experimental conditions designed to induce differentiation into a hepatocyte-like phenotype. Gallbladder epithelial cells (GBEC) cultured under standard conditions exhibited no β-Gal activity. β-Gal expression was prominent in 50% of cells cultured under experimental conditions. Similar morphological changes were observed in GBEC from green fluorescent protein transgenic mice cultured under experimental conditions. These cells showed higher levels of mRNA for genes expressed in hepatocytes, but not in GBEC, including aldolase B, albumin, hepatocyte nuclear factor-4α, aldehyde dehydrogenase 1, and glutamine synthetase, and they synthesized bile acids. Additional functional evidence of a hepatocyte-like phenotype included LDL uptake and enhanced benzodiazepine metabolism. Connexin-32 expression was evident in murine hepatocytes and in cells cultured under experimental conditions, but not in cells cultured under standard conditions. Notch 1, 2, and 3 and Notch ligand Jagged 1 mRNAs were downregulated in these cells compared with cells cultured under standard conditions. CD34, α-fetoprotein, and Sca-1 mRNA were not expressed in cells cultured under standard conditions, suggesting that the hepatocyte-like cells did not arise from hematopoietic stem cells or oval cells. These results point to future avenues for investigation into the potential use of GBEC in the treatment of liver disease.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiologyen_HK
dc.subjectBiliary epitheliumen_HK
dc.subjectCell cultureen_HK
dc.subjectStem cellsen_HK
dc.subjectTransdifferentiationen_HK
dc.subjectTransgenic miceen_HK
dc.titleMurine gallbladder epithelial cells can differentiate into hepatocyte-like cells in vitroen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpgi.00263.2006en_HK
dc.identifier.pmid17717044-
dc.identifier.scopuseid_2-s2.0-36148932552en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36148932552&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume293en_HK
dc.identifier.issue5en_HK
dc.identifier.spageG944en_HK
dc.identifier.epageG955en_HK
dc.identifier.eissn1522-1547-
dc.identifier.isiWOS:000250709000004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKuver, R=6701723533en_HK
dc.identifier.scopusauthoridSavard, CE=6701738621en_HK
dc.identifier.scopusauthoridSung, KL=22986912000en_HK
dc.identifier.scopusauthoridHaigh, WG=6603814152en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK

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