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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Scharenberg, C. W. Articles by Torok-Storb, B. Search for Related Content PubMed PubMed Citation Articles by Scharenberg, C. W. Articles by Torok-Storb, B. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2002, Vol. 99, No. 2, pp. 507-512 HEMATOPOIESIS The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors Christian W. Scharenberg, Michael A. Harkey, and Beverly Torok-Storb From the Divisions of Clinical Research and Basic Sciences, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA. A promising and increasingly exploited property of hematopoietic stem cells is their ability to efflux the fluorescent dye Hoechst 33342. The Hoechst-negative cells are isolated by fluorescence-activated cell sorting as a so-called side "population" (SP) of bone marrow. This SP from bone marrow, as well as other tissues, is reported to contain immature stem cells with considerable plasticity. Some cell lines also efflux Hoechst and generate SP profiles. Reverse transcription-polymerase chain reaction (RT-PCR) and efflux inhibition studies with the lung carcinoma cell line, A549, implicated the ABCG2 transporter as a Hoechst efflux pump. Furthermore, it is shown that transient expression of ABCG2 generates a robust SP phenotype in human embryonic kidney (HEK293) cells. The results allow the conclusion that ABCG2 is a potent Hoechst efflux pump. Semiquantitative RT-PCR was used to characterize the developmental pattern of expression of ABCG2 in hematopoiesis. It is expressed at relatively high levels in putative hematopoietic stem cells (isolated as SP, 34+/38 or 34+/KDR+ populations) and drops sharply in committed progenitors (34+/38+, 34+/33+, or 34+/10+). Expression remains low in most maturing populations, but rises again in natural killer cells and erythroblasts. Comparison of messenger RNA (mRNA) levels for the 3 major multidrug-resistant efflux pumps, MDR1, MRP1, and ABCG2, in bone marrow SP cells reveals that ABCG2 is the predominant form in these cells. These data suggest that ABCG2 contributes significantly to the generation of the SP phenotype in hematopoietic stem cells. Furthermore, the sharp down-regulation of ABCG2 at the stage of lineage commitment suggests that this gene may play an important role in the unique physiology of the pluripotent stem cell. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. van de Ven, R. Oerlemans, J. W. van der Heijden, G. L. Scheffer, T. D. de Gruijl, G. Jansen, and R. J. Scheper ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and cancer J. Leukoc. Biol., November 1, 2009; 86(5): 1075 - 1087. [Abstract] [Full Text] [PDF] M. NOWAK, J. A. MADEJ, and P. DZIEGIEL Expression of Breast Cancer Resistance Protein (BCRP-1) in Canine Mammary Adenocarcinomas and Adenomas In Vivo, September 1, 2009; 23(5): 705 - 709. [Abstract] [Full Text] [PDF] C. Hu, H. Li, J. Li, Z. Zhu, S. Yin, X. Hao, M. Yao, S. Zheng, and J. 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