Non-side-population hematopoietic stem cells in mouse bone marrow

Blood. 2006 Oct 15;108(8):2850-6. doi: 10.1182/blood-2006-03-010207. Epub 2006 Jun 27.

Abstract

Most hematopoietic stem cells (HSCs) are assumed to reside in the so-called side population (SP) in adult mouse bone marrow (BM). We report the coexistence of non-SP HSCs that do not significantly differ from SP HSCs in numbers, capacities, and cell-cycle states. When stained with Hoechst 33342 dye, the CD34(-/low) c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cell population, highly enriched in mouse HSCs, was almost equally divided into the SP and the main population (MP) that represents non-SP cells. Competitive repopulation assays with single or 30 SP- or MP-CD34(-)KSL cells found similar degrees of repopulating activity and frequencies of repopulating cells for these populations. Secondary transplantation detected self-renewal capacity in both populations. SP analysis of BM cells from primary recipient mice suggested that the SP and MP phenotypes are interconvertible. Cell-cycle analyses revealed that CD34(-)KSL cells were in a quiescent state and showed uniform cell-cycle kinetics, regardless of whether they were in the SP or MP. Bcrp-1 expression was similarly detected in SP- and MP-CD34(-)KSL cells, suggesting that the SP phenotype is regulated not only by Bcrp-1, but also by other factors. The SP phenotype does not specify all HSCs; its identity with stem cell function thus is unlikely.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antigens, CD34 / metabolism
  • Antigens, Ly / metabolism
  • Base Sequence
  • Biomarkers / metabolism
  • Bone Marrow Cells / classification*
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Cycle
  • DNA, Complementary / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / classification*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Phenotype
  • Proto-Oncogene Proteins c-kit / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcg2 protein, mouse
  • Antigens, CD34
  • Antigens, Ly
  • Biomarkers
  • DNA, Complementary
  • Ly6a protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins c-kit