The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype
Sheng Zhou1, John D. Schuetz2, Kevin D. Bunting1, Anne-Marie Colapietro1, Janardhan Sampath2, John J. Morris1, Irina Lagutina3, Gerard C. Grosveld3, Mitsujiro Osawa4, Hiromitsu Nakauchi4
& Brian P. Sorrentino1
1
Division of Experimental Hematology, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
2
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
3
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
4
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), Tsukuba, Ibaraki, Japan
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
