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

Stem cells from bone marrow, skeletal muscle and possibly other tissues can be identified by the 'side-population' (SP) phenotype. Although it has bee n assumed that expression of ABC transporters is responsible for this pheno type, the specific molecules involved have not been defined. Here we show t hat expression of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene i s a conserved feature of stem cells from a wide variety of sources. Bcrp1 m RNA was expressed at high levels in primitive murine hematopoietic stem cel ls, 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 transplant ation-based assays. These results show that expression of the Bcrp1/ABCG2 g ene is an important determinant of the SP phenotype, and that it might serv e as a marker for stem cells from various sources.