Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse progeny tracking model.
Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse progeny tracking model.
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DOI:
10.1002/stem.1002
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发表时间:
2012-02
期刊:
影响因子:
--
通讯作者:
Sorrentino BP
中科院分区:
文献类型:
--
作者:
Fatima S;Zhou S;Sorrentino BP
The side population (SP) phenotype is associated with the Hoechst dye efflux activity of the Abcg2 transporter and identifies hematopoietic stem cells (HSCs) in the bone marrow. This association suggests the direct use of Abcg2 expression to identify adult stem cells in various other organs. We have generated a lineage tracing mouse model based on an allele that co-expresses both Abcg2 and a CreERT2 expression cassette. By crossing these mice with lox-STOP-lox reporter lines (LacZ or YFP), cells that express Abcg2 and their progeny were identified following treatment with tamoxifen (Tam). In the liver and kidney, in which mature cells express Abcg2, reporter gene expression verified the expected physiologic expression pattern of the recombinant allele. Long term marking of HSCs was seen in multiple peripheral blood lineages from adult mice, demonstrating that Abcg2+ bone marrow HSCs contribute to steady state hematopoiesis. Stem cell tracing patterns were seen in the small intestine and in seminiferous tubules in the testis twenty months after Tam treatment, proving that stem cells from these organs express Abcg2. Interstitial cells from skeletal and cardiac muscle were labeled and some cells co-stained with endothelial markers, raising the question as to whether these may function as tissue-specific muscle stem cells. Altogether, these studies prove that Abcg2 is a stem cell marker for blood, small intestine, and testicular germ cells and provide a new model for studying stem cell activity that does not require transplant-based assays.