Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1.
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.
Shimano
Koichi
K
Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Satake
Makoto
M
Okaya
Atsuhito
A
Kitanaka
Junichi
J
Kitanaka
Nobue
N
Takemura
Motohiko
M
Sakagami
Masafumi
M
Terada
Nobuyuki
N
Tsujimura
Tohru
T
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D006498:Hepatectomy; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014018:Tissue Distribution
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D002273:Carcinogens; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D015073:2-Acetylaminofluorene; C017807:bisbenzimide ethoxide trihydrochloride