title: Non-side-population hematopoietic stem cells in mouse bone marrow.
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.
authors.affiliation: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639 Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Morita
authors.forename: Hideo
authors.initials: H
authors.lastname: Ema
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000145:classification* / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle; D018076:DNA, Complementary / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D018952:Antigens, CD34; D000950:Antigens, Ly; D015415:Biomarkers; D018076:DNA, Complementary; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit