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The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype

Nature Medicine volume 7, pages 1028–1034 (2001)Cite this article

Abstract

Stem cells from bone marrow, skeletal muscle and possibly other tissues can be identified by the 'side-population' (SP) phenotype. Although it has been assumed that expression of ABC transporters is responsible for this phenotype, the specific molecules involved have not been defined. Here we show that expression of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene is a conserved feature of stem cells from a wide variety of sources. Bcrp1 mRNA was expressed at high levels in primitive murine hematopoietic stem cells, and was sharply downregulated with differentiation. Enforced expression of the ABCG2 cDNA directly conferred the SP phenotype to bone-marrow cells and caused a reduction in maturing progeny both in vitro and in transplantation-based assays. These results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.

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Figure 1: SP-cell analyses of bone-marrow cells from wild-type and Mdr1a/1b−/− mice.
Figure 2: Analyses of ABC transporters expressed in sorted SP cells.
Figure 3: RT-PCR analyses of transporter gene expression in primitive CD34− murine stem cells.
Figure 4: RT-PCR analyses for Bcrp1/ABCG2 expression in sorted SP cells from rhesus monkey bone marrow, mouse skeletal muscle and murine ES cells.
Figure 5: SP cell phenotype in cells transduced with ABCG2 vectors.
Figure 6: Functional effects of enforced ABCG2 expression in murine hematopoietic cells.

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Acknowledgements

We thank P. Bois for providing the cDNA samples from sorted skeletal muscle SP cells; R. Ashmun for help in performing the SP assays; O. Lagutin and G. Oliver for providing specific ES cell lines for study; A. Wall for help with ABCG2 vectors; G. Kruh for his generous gift of MRP3-expressing cells; and V. D'Hondt for her gift of MRP1-expressing cells. This work was supported in part by P01 HL 53749 (to B.P.S.), R01 HL67366-01 (to B.P.S.), ASSISI Foundation of Memphis Grant 94-00 (to B.P.S.), ES05851 (to J.S.), GM60904 (to J.S.), Cancer Center Support Grant P30 CA21765, and the American Lebanese Syrian Associated Charities.

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Authors and Affiliations

  1. Division of Experimental Hematology, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Sheng Zhou, Kevin D. Bunting, Anne-Marie Colapietro, John J. Morris & Brian P. Sorrentino

  2. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    John D. Schuetz & Janardhan Sampath

  3. Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Irina Lagutina & Gerard C. Grosveld

  4. Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), Tsukuba, Ibaraki, Japan

    Mitsujiro Osawa & Hiromitsu Nakauchi

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  1. Sheng Zhou
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Correspondence to Brian P. Sorrentino.

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Zhou, S., Schuetz, J., Bunting, K. et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7, 1028–1034 (2001). https://doi.org/10.1038/nm0901-1028

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