Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1
Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1
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DOI：
10.1016/s0002-9440(10)63624-3
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发表时间：
2003-07-01
影响因子：
6
通讯作者：
Tsujimura, T
中科院分区：
文献类型：
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作者：
Shimano, K;Satake, M;Tsujimura, T
器官特异性干细胞可以通过侧群 (SP) 表型来识别，该表型是通过有效排除 Hoechst 33342 染料的特性来定义的。 ATP 结合盒转运蛋白 ABCG2/BCRP1 介导 SP 表型。由于肝卵圆细胞具有干细胞的几个特征，因此我们使用2-乙酰氨基芴/部分肝切除（PH）模型检查了它们是否具有SP表型。荧光激活细胞分选分析表明，在 PH 后第 7 天制备的含有卵圆细胞的非实质细胞群携带大量 SP 细胞，而在 PH 后第 0 天制备的不含卵圆细胞的非实质细胞则没有。使用PH后各天获得的总肝脏RNA进行Northern印迹分析表明，ABCG2/BCRP1 mRNA的表达在PH后增加，在第7天达到最高水平，然后逐渐下降。 ABCG2/BCRP1 mRNA 水平的这种变化模式与卵圆细胞数量的变化密切相关。此外，原位杂交显示卵圆细胞是 ABCG2/BCRP1 mRNA 的表达位点。这些结果表明卵圆细胞具有由 ABCG2/BCRPI 表达定义的 SP 表型，表明卵圆细胞可能代表肝脏中的干细胞。
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/BCRPI, suggesting that oval cells may represent stem cells in the liver.