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(American Journal of Pathology. 2003;163:3-9.)
© 2003 American Society for Investigative Pathology


Short Communication

Hepatic Oval Cells Have the Side Population Phenotype Defined by Expression of ATP-Binding Cassette Transporter ABCG2/BCRP1

Koichi Shimano*{dagger}, Makoto Satake*{ddagger}, Atsuhito Okaya*{ddagger}, Junichi Kitanaka§, Nobue Kitanaka§, Motohiko Takemura§, Masafumi Sakagami{dagger}, Nobuyuki Terada* and Tohru Tsujimura*

From the Departments of Pathology,* Otolaryngology,{dagger} Surgery,{ddagger} and Pharmacology,§ Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

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.





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