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 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.
Zhou
S
S
Division of Experimental Hematology, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Schuetz
J D
JD
Bunting
K D
KD
Colapietro
A M
AM
Sampath
J
J
Morris
J J
JJ
Lagutina
I
I
Grosveld
G C
GC
Osawa
M
M
Nakauchi
H
H
Sorrentino
B P
BP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D019742:Chemokines, CC; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012269:Ribosomal Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D060245:Tetraspanin 29; D019737:Transplants
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D019742:Chemokines, CC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012269:Ribosomal Proteins; D060245:Tetraspanin 29; C073492:ABCC4 protein, human; C116614:ABCG2 protein, human; C489540:Abcc4 protein, mouse; C554869:CD9 protein, human; C095218:Ccl9 protein, mouse; C554870:Cd9 protein, mouse