Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1

Am J Pathol. 2003 Jul;163(1):3-9. doi: 10.1016/S0002-9440(10)63624-3.


Organ-specific stem cells can be identified by the side population (SP) phenotype, which is defined by the property to effectively exclude the Hoechst 33342 dye. The ATP-binding cassette transporter ABCG2/BCRP1 mediates the SP phenotype. Because hepatic oval cells possess several characteristics of stem cells, we examined whether they have the SP phenotype using the 2-acetylaminofluorene/partial hepatectomy (PH) model. Fluorescence-activated cell sorting analysis showed that a population of non-parenchymal cells containing oval cells, prepared on day 7 after PH, carried a significant number of SP cells, whereas that of non-parenchymal cells without oval cells, prepared on day 0 after PH, did not. Northern blot analysis using total liver RNA obtained on various days after PH showed that the expression of ABCG2/BCRP1 mRNA increased after PH, reaching the highest level on day 7, and then gradually decreased. This pattern of changes in the ABCG2/BCRP1 mRNA level was well correlated to that in the number of oval cells. Furthermore, in situ hybridization revealed that oval cells were the sites of expression of ABCG2/BCRP1 mRNA. These results indicate that oval cells have the SP phenotype defined by expression of ABCG2/BCRP1, suggesting that oval cells may represent stem cells in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / pharmacology
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Benzimidazoles / metabolism
  • Carcinogens / pharmacology
  • Fluorescent Dyes / metabolism
  • Hepatectomy
  • In Situ Hybridization
  • Liver / cytology*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Tissue Distribution


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Benzimidazoles
  • Carcinogens
  • Fluorescent Dyes
  • Neoplasm Proteins
  • 2-Acetylaminofluorene
  • bisbenzimide ethoxide trihydrochloride