Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Stem Cell Procurement

Side population/ABCG2-positive cells represent a heterogeneous group of haemopoietic cells: implications for the use of adult stem cells in transplantation and plasticity protocols

Summary:

Murine side population (SP) cells may have an increased ability to engraft lethally irradiated mice and lack CD34 expression. Strategies using CD34 as a primary marker of haemopoietic stem cells may therefore result in the exclusion of a primitive stem cell population. The molecular basis for the murine SP phenotype has been attributed to the multidrug-resistance transporter ABCG2. This study aimed to investigate ABCG2 expression from a variety of human sources and investigate the relationship between ABCG2 expression, the SP phenotype, and expression of markers such as CD34 and CD133. SP cells were observed in different haemopoietic sources, but a significant increase in the number of SP cells was observed in PB following granulocyte colony-stimulating factor mobilisation. No direct correlation between the frequency of SP cells and the expression of ABCG2 was observed. SP cells were identified in both lineage-positive and lineage-negative population and ABCG2 expression was enriched in lineage-negative SP cells. Lineage-negative SP cells were devoid of CD34 expression but enriched for CD133. Subsequent analysis revealed that ABCG2 and CD133 are coexpressed. Together, these data suggest that the ABCG2 transporter is neither required nor responsible for the SP phenotpye in many human blood cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Civin CI, Strauss LC, Brovall C et al. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol 1984; 133: 157–165.

    CAS  PubMed  Google Scholar 

  2. Osawa M, Hanada K, Hamada H, Nakauchi H . Longterm lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996; 273: 242–245.

    Article  CAS  PubMed  Google Scholar 

  3. Bhatia M, Bonnet D, Murdoch B et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 1998; 4: 1038–1045.

    Article  CAS  PubMed  Google Scholar 

  4. Gussoni E, Soneoka Y, Strickland CD et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390–394.

    CAS  PubMed  Google Scholar 

  5. Lagasse E, Connors H, Al-Dhalimy M et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 6: 1229–1234.

    Article  CAS  PubMed  Google Scholar 

  6. Goodell MA, Brose K, Paradis G et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996; 183: 1797–1806.

    Article  CAS  PubMed  Google Scholar 

  7. Jackson KA, Majka SM, Wang H et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107: 1395–1402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uchida N, Fujisaki T, Eaves AC, Eaves CJ . Transplantable hematopoietic stem cells in human fetal liver have a CD34(+) side population (SP)phenotype. J Clin Invest 2001; 108: 1071–1077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Storms RW, Goodell MA, Fisher A et al. Hoechst dye efflux reveals a novel CD7(+)CD34(−) lymphoid progenitor in human umbilical cord blood. Blood 2000; 96: 2125–2133.

    CAS  PubMed  Google Scholar 

  10. Feuring-Buske M, Hogge DE . Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(−) progenitor cells from patients with acute myeloid leukemia. Blood 2001; 97: 3882–3889.

    Article  CAS  PubMed  Google Scholar 

  11. Wulf GG, Wang RY, Kuehnle I et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001; 98: 1166–1173.

    Article  CAS  PubMed  Google Scholar 

  12. Preffer FI, Dombkowski D, Sykes M et al. Lineage-negative side-population (SP) cells with restricted hematopoietic capacity circulate in normal human adult blood: immunophenotypic and functional characterization. Stem Cells 2002; 20: 417–427.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou S, Schuetz JD, Bunting KD 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 2001; 7: 1028–1034.

    Article  CAS  PubMed  Google Scholar 

  14. Scharenberg CW, Harkey MA, Torok-Storb B . The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 2002; 99: 507–512.

    Article  CAS  PubMed  Google Scholar 

  15. Goodell MA, Rosenzweig M, Kim H et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 1997; 3: 1337–1345.

    Article  CAS  PubMed  Google Scholar 

  16. Asakura A, Rudnicki MA . Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. Exp Hematol 2002; 30: 1339–1345.

    Article  PubMed  Google Scholar 

  17. Zhou S, Morris JJ, Barnes Y et al. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci USA 2002; 99: 12339–12344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gallacher L, Murdoch B, Wu DM, Karanu FN, Keeney M, Bhatia M . Isolation and characterization of human CD34(−)Lin(−) and CD34(+)Lin(−) hematopoietic stem cells using cell surface markers AC133 and CD7. Blood 2000; 95: 2813–2820.

    CAS  PubMed  Google Scholar 

  19. Abbott BL, Colapietro AM, Barnes Y et al. Low levels of ABCG2 expression in adult AML blast samples. Blood 2002; 100: 4594–4601.

    Article  CAS  PubMed  Google Scholar 

  20. Satterthwaite AB, Borson R, Tenen D . Regulation of the gene for CD34, a human hematopoietic stem cell antigen, in KG-1 cells. Blood 1990; 75 (12): 2299–2304.

    Google Scholar 

Download references

Acknowledgements

We thank Jon Murray, Angela Good and Rita Angelica, the Transplant Co-ordinators from the Adult Leukaemia Unit, Christie Hospital NHS Trust, Manchester. Umbilical Cord Blood was obtained with the kind assistance of staff at Manchester Royal Infirmary, Bolton Royal Infirmary, Victoria Royal Infirmary, Newcastle upon Tyne and Southmead Hospital, Bristol. Finally, We thank Mike Hughes and Jeff Barry, Paterson Institute for Cancer Research, for help with flow cytometry.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Chopra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naylor, C., Jaworska, E., Branson, K. et al. Side population/ABCG2-positive cells represent a heterogeneous group of haemopoietic cells: implications for the use of adult stem cells in transplantation and plasticity protocols. Bone Marrow Transplant 35, 353–360 (2005). https://doi.org/10.1038/sj.bmt.1704762

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704762

Keywords

This article is cited by

Search

Quick links