title: Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment.
abstract: Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and in vivo behavior. We attempted prospective isolation of HSC subsets with distinct properties among CD34(-/low) c-Kit+Sca-1+Lin- (CD34-KSL) cells. CD34-KSL cells were divided, based on CD150 expression, into three fractions: CD150high, CD150med, and CD150neg cells. Compared with the other two fractions, CD150high cells were significantly enriched in HSCs, with great self-renewal potential. In vitro colony assays revealed that decreased expression of CD150 was associated with reduced erythroblast/megakaryocyte differentiation potential. All three fractions were regenerated only from CD150high cells in recipient mice. Using single-cell transplantation studies, we found that a fraction of CD150high cells displayed latent and barely detectable myeloid engraftment in primary-recipient mice but progressive and multilineage reconstitution in secondary-recipient mice. These findings highlight the complexity and hierarchy of reconstitution capability, even among HSCs in the most primitive compartment.
authors.affiliation: Division of Stem Cell Therapy and FACS Core Laboratory, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 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: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D015415:Biomarkers / Q000378:metabolism; D002451:Cell Compartmentation; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012038:Regeneration; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019009:Proto-Oncogene Proteins c-kit